Kits and methods for nutrition supplementation

ABSTRACT

The present invention relates to methods of co-administration of various vitamin and mineral compositions, and in a specific embodiment, said methods comprise co-administering one composition comprising vitamin A, beta carotene, B-complex vitamins, vitamin C, vitamin D 3 , vitamin E, iron, magnesium and zinc, and a second composition comprising omega-3 fatty acids such as DHA, to supplement the nutritional needs of individuals within physiologically stressful states; and kits provided for co-administration of various vitamin and mineral compositions, and in a specific embodiment, said kits comprise one composition comprising vitamin A, beta carotene, B-complex vitamins, vitamin C, vitamin D 3 , vitamin E, iron, magnesium and zinc, and a second composition comprising omega-3 fatty acids such as DHA, to supplement the nutritional needs of individuals within physiologically stressful states.

CROSS REFERENCE TO RELATED APPLICATIONS

This application is a continuation patent application and claims thebenefit, under 35 U.S.C. §120, of U.S. patent application Ser. No.14/106,916, filed Dec. 16, 2013, which is a continuation of U.S. patentapplication Ser. No. 13/356,247, filed Jan. 23, 2012, now U.S. Pat. No.8,609,629, issued Dec. 17, 2013, which is a continuation of U.S. patentapplication Ser. No. 12/422,091, filed Apr. 10, 2009, now U.S. Pat. No.8,101,587, issued Jan. 24, 2012, which is a continuation-in-part andclaims the benefit under 35 U.S.C. §120, of U.S. patent application Ser.No. 11/928,610, filed Oct. 30, 2007, now U.S. Pat. No. 8,197,855, issuedJun. 12, 2012, which is a continuation and claims the benefit under 35U.S.C. §120, of U.S. patent application Ser. No. 10/916,534, filed Aug.12, 2004, now U.S. Pat. No. 7,560,123, issued Jul. 14, 2009. The entirecontents and substance of each of the foregoing patents and patentapplications are hereby incorporated by reference.

FIELD OF THE INVENTION

The present invention relates to methods of co-administration of variousvitamin and mineral compositions and kits provided for co-administrationof these compositions for nutritional supplementation in, for example,subjects in physiologically stressful states.

BACKGROUND OF THE INVENTION

Nutrition plays a critical role in maintaining good health. Propernutrition prevents dietary deficiencies, and also protects against thedevelopment of disease. When the body faces physiological stress, propernutrition plays an increasingly important role. For example, pregnancyand lactation are among the most nutritionally volatile andphysiologically stressful periods and processes in the lifetimes ofwomen. Vitamin and mineral needs are almost universally increased duringthese natural processes. Increased vitamin and mineral needs duringthese times are almost always due to elevated metabolic demand,increased plasma volume, increased levels of blood cells, decreasedconcentrations of nutrients, and decreased concentrations ofnutrient-binding proteins.

When increased nutrient needs occur during pregnancy, lactation, or anyother physiologically stressful state, nutritional supplementationserves a vital role in maintaining good health. Nutritionalsupplementation is especially pertinent to women contemplatingconceiving a child because optimizing specific nutrients before, during,and after the physiological processes of pregnancy or lactation can haveprofound, positive, and comprehensive impacts upon the overall wellnessof the developing and newborn child as well as on the safety and healthof the mother. The present invention provides kits and methods designedto supplement the nutritional needs of individuals in physiologicallystressful states.

Supplementation with certain vitamins and minerals serves a role inprotecting against disease and contributes to the overall health of themother and developing child. Specifically, such compounds as vitamin B₆,vitamin B₁₂, vitamin B₉, and omega-3 fatty acids such as docosahexaenoicacid (DHA), play integral roles in physiological mechanisms that serveto prevent, treat and/or alleviate the occurrence or negative effects ofsome diseases.

DHA specifically has shown multiple health-promoting properties inadults. These include anti-thrombotic, anti-inflammatory andanti-atherosclerotic activity, all of which reduce the risk of heartdisease. M Laidlaw and B J Holub, AM J CLIN NUTR 77:37-42 (2003).Inverse relationships have also been found between systemic levels ofDHA and incidence and severity of mood disorders and depression,including post-partum depression. Therefore, introduction of omega-3fatty acids such as DHA during pregnancy has a double benefit, to bothchild and mother.

Supplementation of other vitamins and minerals with DHA, however, mayinhibit DHA's beneficial effects, for example, inhibiting the beneficialeffects of reducing the incidence of post-partum depression. Indeed,high blood serum levels of copper, a mineral that is often included innutritional supplements, has been associated with post-partumdepression. J W Crayton et al., J TRACE ELEM MED BIOL 21(1): 17-21(2007).

Other vitamins and minerals that provide certain benefits may also beassociated with undesirable side effects, and thus, would preferably beexcluded from a nutritional supplement. For example, calcium, a mineralthat is often included in nutritional supplements, has been linked toconstipation and other stomach problems such as nausea, vomiting andcramps.

A nutritional supplement kit for physiological stressful states such asduring pregnancy or during lactation that includes the benefits of DHA,but excludes the vitamins and minerals that can either have deleteriouseffects on DHA's benefits, or other unappealing side effects, iscurrently needed.

SUMMARY OF THE INVENTION

The present invention provides methods of co-administering compositionsand kits comprising compositions for both prophylactic and therapeuticnutritional supplementation. Specifically, for example, the presentinvention relates to novel compositions of vitamins and minerals thatcan be used to supplement the nutritional deficiencies observed inpatients throughout physiologically stressful states. The presentinvention also may be formulated to exclude vitamins and minerals knownto inhibit the beneficial effects of the included vitamins and mineralsor cause other undesirable side effects.

The present invention includes methods of co-administering thecompositions of the invention to patients, together or in any order, tosupplement the nutritional deficiencies observed in patients throughoutphysiologically stressful states such as, for example, pregnancy,lactation, and any disease state. The compositions of the presentinvention may be in a swallowable, chewable or dissolvable formaccording to an individual patient's preference. Choice in dosage formpromotes ease of administration and compliance with dosing regimens.

The present invention also includes kits that may be provided topatients, wherein the compositions as described herein are packaged forco-administration to a patient.

In one embodiment of the present invention, the methods may compriseco-administering to a patient a first composition comprising vitamin A,beta carotene, vitamin B₁, vitamin B₂, vitamin B₃, vitamin B₆, vitaminB₉, vitamin B₁₂, vitamin C, vitamin D₃, vitamin E, iron, magnesium andzinc to a patient and a second composition comprising omega-3 fattyacids to the patient. In another embodiment, the methods and kits maycomprise a second composition wherein omega-3 fatty acids comprisedocahexaenoic acid (DHA). In another embodiment, the docahexaenoic acidis derived from algae.

In one embodiment, the methods may comprise co-administering the twocompositions at the same time, or one after the other in either order.In a specific embodiment, the compositions of the described method maybe co-administered to the patient orally.

In another specific embodiment of the methods and kits, the compositionsmay be swallowable, chewable, or dissolvable. In another embodiment, thefirst composition is in a different form than the second composition.

In another specific embodiment of the methods and kits of the presentinvention, vitamin A comprises acetate. In another specific embodiment,vitamin B₁ comprises thiamine mononitrate. In another specificembodiment, vitamin B₃ comprises niacinamide. In another specificembodiment, vitamin B₆ comprises pyridoxine hydrochloride. In anotherspecific embodiment, vitamin B₉ comprises one or more of the groupconsisting of folic acid, folacin, metafolin, and folate. In anotherspecific embodiment, vitamin B₉ comprises one or more naturalderivatives of folate selected from the group consisting of(6S)-tetrahydrofolic acid or a polyglutamyl derivative thereof,5-methyl-(6S)-tetrahydrofolic acid or a polyglutamyl derivative thereof,5-formyl-(6S)-tetrahydrofolic acid or a polyglutamyl derivative thereof,10-formyl-(6R)-tetrahydrofolic acid or a polyglutamyl derivativethereof, 5,10-methylene-(6R)-tetrahydrofolic acid or a polyglutamylderivative thereof, 5,10-methenyl-(6R)-tetrahydrofolic acid or apolyglutamyl derivative thereof, and 5-formimino-(6S)-tetrahydrofolicacid or a polyglutamyl derivative thereof. In another specificembodiment, vitamin B₁₂ comprises cyanocobalamin. In another specificembodiment, vitamin C comprises ascorbic acid. In another specificembodiment, vitamin E comprises d-alpha tocopheryl acetate. In anotherspecific embodiment, iron comprises polysaccharide iron complex. Inanother specific embodiment, magnesium comprises magnesium oxide. Inanother specific embodiment, zinc comprises zinc oxide.

In another specific embodiment of the methods and kits of the presentinvention, the first composition may be substantially free of one ormore of added compounds selected from the group consisting of vitamin A,beta carotene, vitamin B₁, vitamin B₂, vitamin B₃, vitamin B₆, vitaminB₉, vitamin B₁₂, vitamin C, vitamin D₃, vitamin E, iron, magnesium andzinc.

In another embodiment of the methods and kits of the present invention,first and second compositions may be substantially free of one or moreof added active compounds selected from the group consisting of lutein,lycopene, zeaxanthin, vitamin B₄, vitamin B₅, vitamin B₇, vitamin B₈,vitamin B₁₀, vitamin K, biotin, pantothenic acid, phosphorus, iodine,potassium, odorless garlic, coenzyme Q₁₀, l-carnitine, grape seedextract, chloride, sodium, green tea extract, quercetin, fluoride,hawthorne berries, and alpha lipoic acid. In another embodiment of themethods of the present invention, the first and second compositions maybe substantially free of one or more of added minerals and compoundsselected from the group consisting of, copper, calcium, chromium,titanium, molybdenum, nickel, tin, silicon, vanadium, manganese,selenium, selenite, boron, bismuth, borax, bauxite, gold, silver,hydroxylapatite, mica, quartz, steatite, talc, sulfur, and zircon. Inanother embodiment of the methods and kits of the present invention, thefirst and second compositions may be substantially free of one or moreof added inactive compounds selected from the group consisting ofmagnesium stearate, silica, silicon dioxide, magnesium silicate,dicalcium phosphate, povidone, titanium dioxide, sodium benzoate, alphalipoic acid, lutein, lycopene, cellulose, croscarmellose sodium, stearicacid, cellulose, hydroxylpropyl cellulose, hydroxypropylmethylcellulose, titanium dioxide, polydextrose, triacetin, dicalciumphosphate, polyethylene glycol, polyvinylpyrrolidone, mineral oil,methocel, sodium lauryl sulfate, and talc.

In another specific embodiment, the methods and kits may include acomposition further comprising a pharmaceutically acceptable carrier. Inanother specific embodiment, the methods and kits may include the firstcomposition further comprising a pharmaceutically acceptable carrier. Inanother specific embodiment, the methods and kits may include the secondcomposition further comprising a pharmaceutically acceptable carrier. Inanother specific embodiment of the present invention, thepharmaceutically acceptable carrier is one or more selected from thegroup consisting of binders, diluents, lubricants, glidants, colorants,emulsifiers, disintegrants, starches, water, oils, alcohols,preservatives and sugars.

In another specific embodiment, the methods and kits may include thefirst composition further comprising a sweetening agent and the secondcomposition further comprising a sweetening agent. In another specificembodiment, the first composition may further comprise a flavorant andthe second composition further comprising a flavorant.

In another specific embodiment of the methods and kits of the presentinvention, the first composition may comprise about 550 IU to about 1650IU of vitamin A; about 300 IU to about 900 IU beta carotene; about 200IU to about 600 IU of vitamin D₃; about 30 mg to about 90 mg of vitaminC; about 15 IU to about 45 IU of vitamin E; about 0.5 mg to about 1.5 mgof vitamin B₉; about 1.0 mg to about 3.0 mg of vitamin B₁; about 1.0 mgto about 3.0 mg of vitamin B₂; about 7.0 mg to about 23 mg of vitaminB₃; about 1.0 mg to about 4.0 mg of vitamin B₆; about 2.0 mcg to about8.0 mcg of vitamin B₁₂; about 14 mg to about 44 mg of iron; about 12 mgto about 38 mg of magnesium; and about 7.0 mg to about 23 mg of zinc. Inanother specific embodiment of the methods and kits of the presentinvention, the first composition may comprise about 1100 IU of vitaminA; about 600 IU beta carotene; about 400 IU of vitamin D₃; about 60 mgof vitamin C; about 30 IU of vitamin E; about 1.0 mg of vitamin B₉;about 1.6 mg of vitamin B₁; about 1.8 mg of vitamin B₂; about 15 mg ofvitamin B₃; about 2.5 mg of vitamin B₆; about 5.0 mcg of vitamin B₁₂;about 29 mg of iron; about 25 mg of magnesium; and about 15 mg of zinc.

In another specific embodiment of the methods and kits of the presentinvention, omega-3 fatty acids may be present in the amount of about 125mg to about 375 mg. In another embodiment, omega-3 fatty acids may bepresent in the amount of about 200 mg to about 300 mg. In anotherembodiment, omega-3 fatty acids may be present in the amount of about225 mg to about 275 mg. In another embodiment, omega-3 fatty acids maybe present in the amount of about 250 mg. In another embodiment, theomega-3 fatty acids may be enclosed within a gel-cap. In anotherembodiment, the second composition may be in liquid form.

In another embodiment of the present invention the kits may comprise: afirst composition comprising vitamin A, beta carotene, vitamin B₁,vitamin B₂, vitamin B₃, vitamin B₆, vitamin B₉, vitamin B₁₂, vitamin C,vitamin D₃, vitamin E, iron, magnesium and zinc; and a secondcomposition comprising omega-3 fatty acids; wherein the first and secondcompositions are packaged for co-administration to a patient, in anyorder.

In another embodiment, the kits are packaged in various forms includingbottles and blister packs.

In yet another embodiment, the kits may be packaged in bottles that aresold together; one bottle containing compositions comprising vitamin A,beta carotene, vitamin B₁, vitamin B₂, vitamin B₃, vitamin B₆, vitaminB₉, vitamin B₁₂, vitamin C, vitamin D₃, vitamin E, iron, magnesium andzinc; and one bottle containing compositions comprising omega-3 fattyacids such as DHA.

In yet another embodiment, the kits may be packaged in bottles that aresold separately; one bottle containing compositions comprising vitaminA, beta carotene, vitamin B₁, vitamin B₂, vitamin B₃, vitamin B₆,vitamin B₉, vitamin B₁₂, vitamin C, vitamin D₃, vitamin E, iron,magnesium and zinc; and one bottle containing compositions comprisingomega-3 fatty acids such as DHA.

In an alternative embodiment, the kits may be packaged in bottlesadvertised as more effective if co-administered; one bottle containingcompositions comprising vitamin A, beta carotene, vitamin B₁, vitaminB₂, vitamin B₃, vitamin B₆, vitamin B₉, vitamin B₁₂, vitamin C, vitaminD₃, vitamin E, iron, magnesium and zinc; and one bottle containingcompositions comprising omega-3 fatty acids such as DHA. Theadvertisements may consist of internet, print, and product packagingadvertisements.

In another embodiment, the kits may be packaged in blister packs thatare sold together: one blister pack containing compositions comprisingvitamin A, beta carotene, vitamin B₁, vitamin B₂, vitamin B₃, vitaminB₆, vitamin B₉, vitamin B₁₂, vitamin C, vitamin D₃, vitamin E, iron,magnesium and zinc; and one blister pack containing compositionscomprising omega-3 fatty acids such as DHA.

In yet another embodiment, the kits may be packaged in one blister pack:containing compositions comprising vitamin A, beta carotene, vitamin B₁,vitamin B₂, vitamin B₃, vitamin B₆, vitamin B₉, vitamin B₁₂, vitamin C,vitamin D₃, vitamin E, iron, magnesium and zinc; and containingcompositions comprising omega-3 fatty acids such as DHA.

In another embodiment, the kits may be packaged in blister packs thatare sold separately; one blister pack containing compositions comprisingvitamin A, beta carotene, vitamin B₁, vitamin B₂, vitamin B₃, vitaminB₆, vitamin B₉, vitamin B₁₂, vitamin C, vitamin D₃, vitamin E, iron,magnesium and zinc; and one blister pack containing compositionscomprising omega-3 fatty acids such as DHA.

In yet another embodiment, the kits may be packaged in blister packsadvertised as more effective if co-administered: one blister packcontaining compositions comprising vitamin A, beta carotene, vitamin B₁,vitamin B₂, vitamin B₃, vitamin B₆, vitamin B₉, vitamin B₁₂, vitamin C,vitamin D₃, vitamin E, iron, magnesium and zinc; and one blister packcontaining compositions comprising omega-3 fatty acids such as DHA. Theadvertisements may consist of internet, print, and product packagingadvertisements.

In another embodiment, the invention comprises a method which comprisesproviding the kit as described to patients.

In one embodiment of the present invention, the methods may compriseco-administering to a patient a first composition consisting of vitaminA, beta carotene, vitamin B₁, vitamin B₂, vitamin B₃, vitamin B₆,vitamin B₉, vitamin B₁₂, vitamin C, vitamin D₃, vitamin E, iron,magnesium, zinc and one or more pharmaceutically acceptable carriers toa patient; and a second composition consisting of DHA and one or morepharmaceutically acceptable carriers to said patient. In anotherembodiment, the first composition may consist of about 550 IU to about1650 IU of vitamin A; about 300 IU to about 900 IU beta carotene; about200 IU to about 600 IU of vitamin D₃; about 30 mg to about 90 mg ofvitamin C; about 15 IU to about 45 IU of vitamin E; about 0.5 mg toabout 1.5 mg of vitamin B₉; about 1.0 mg to about 3.0 mg of vitamin B₁;about 1.0 mg to about 3.0 mg of vitamin B₂; about 7.0 mg to about 23 mgof vitamin B₃; about 1.0 mg to about 4.0 mg of vitamin B₆; about 2.0 mcgto about 8.0 mcg of vitamin B₁₂; about 14 mg to about 44 mg of iron;about 12 mg to about 38 mg of magnesium; about 7.0 mg to about 23 mg ofzinc and one or more pharmaceutically acceptable carriers; and thesecond composition may consist of about 125 mg to about 375 mg of DHAand one or more pharmaceutically acceptable carriers. In anotherembodiment, the first composition may consist of about 1100 IU ofvitamin A; about 600 IU beta carotene; about 400 IU of vitamin D₃; about60 mg of vitamin C; about 30 IU of vitamin E; about 1.0 mg of vitaminB₉; about 1.6 mg of vitamin B₁; about 1.8 mg of vitamin B₂; about 15 mgof vitamin B₃; about 2.5 mg of vitamin B₆; about 5.0 mcg of vitamin B₁₂;about 29 mg of iron; about 25 mg of magnesium; about 15 mg of zinc andone or more pharmaceutically acceptable carriers; and the secondcomposition may consist of about 250 mg of DHA and one or morepharmaceutically acceptable carriers.

In another embodiment of the present invention, the kits may comprise: afirst composition consisting of vitamin A, beta carotene, vitamin B₁,vitamin B₂, vitamin B₃, vitamin B₆, vitamin B₉, vitamin B₁₂, vitamin C,vitamin D₃, vitamin E, iron, magnesium, zinc and one or morepharmaceutically acceptable carriers; and a second compositionconsisting of DHA and one or more pharmaceutically acceptable carriers;wherein the first and second compositions are packaged foradministration to a patient, in any order. In another embodiment, thefirst composition may consist of about 550 IU to about 1650 IU ofvitamin A; about 300 IU to about 900 IU beta carotene; about 200 IU toabout 600 IU of vitamin D₃; about 30 mg to about 90 mg of vitamin C;about 15 IU to about 45 IU of vitamin E; about 0.5 mg to about 1.5 mg ofvitamin B₉; about 1.0 mg to about 3.0 mg of vitamin B₁; about 1.0 mg toabout 3.0 mg of vitamin B₂; about 7.0 mg to about 23 mg of vitamin B₃;about 1.0 mg to about 4.0 mg of vitamin B₆; about 2.0 mcg to about 8.0mcg of vitamin B₁₂; about 14 mg to about 44 mg of iron; about 12 mg toabout 38 mg of magnesium; about 7.0 mg to about 23 mg of zinc and one ormore pharmaceutically acceptable carriers; and the second compositionmay consist of about 125 mg to about 375 mg of DHA and one or morepharmaceutically acceptable carriers. In another embodiment, the firstcomposition may consist of about 1100 IU of vitamin A; about 600 IU betacarotene; about 400 IU of vitamin D₃; about 60 mg of vitamin C; about 30IU of vitamin E; about 1.0 mg of vitamin B₉; about 1.6 mg of vitamin B₁;about 1.8 mg of vitamin B₂; about 15 mg of vitamin B₃; about 2.5 mg ofvitamin B₆; about 5.0 mcg of vitamin B₁₂; about 29 mg of iron; about 25mg of magnesium; about 15 mg of zinc and one or more pharmaceuticallyacceptable carriers; and the second composition may consist of about 250mg of DHA and one or more pharmaceutically acceptable carriers. Inanother embodiment, the invention comprises a method which comprisesproviding the kit as described to patients.

Other objectives, features and advantages of the present invention willbecome apparent from the following detailed description. The detaileddescription and the specific examples, although indicating specificembodiments of the invention, are provided by way of illustration only.Accordingly, the present invention also includes those various changesand modifications within the spirit and scope of the invention that maybecome apparent to those skilled in the art from this detaileddescription.

DETAILED DESCRIPTION OF THE INVENTION

It is understood that the present invention is not limited to theparticular methodologies, protocols, fillers, and excipients, etc.,described herein, as these may vary. It is also to be understood thatthe terminology used herein is used for the purpose of describingparticular embodiments only, and is not intended to limit the scope ofthe present invention. It must be noted that as used herein and in theappended claims, the singular forms “a,” “an,” and “the” include theplural reference unless the context clearly dictates otherwise. Thus,for example, a reference to “a vitamin” is a reference to one or morevitamins and includes equivalents thereof known to those skilled in theart and so forth.

Unless defined otherwise, all technical and scientific terms used hereinhave the same meanings as commonly understood by one of ordinary skillin the art to which this invention belongs. Specific methods, devices,and materials are described, although any methods and materials similaror equivalent to those described herein can be used in the practice ortesting of the present invention. All references cited herein areincorporated by reference herein in their entirety.

The term “disease state” as used herein, may comprise any state in whichone or more organs or components of an organism malfunction. The term“disease state” may refer to any deterioration of any component of abody. The term “disease state” may refer to any deficiency of anycompound necessary for the maintenance or function of any component ofany organism. The term “disease state” may refer to any condition inwhich a body contains toxins, produced by microorganisms that infect thebody or by body cells through faulty metabolism or absorbed from anexternal source. “Disease states” may be adverse states caused by anydiet, any virus, or any bacteria. “Disease states” may comprisedisorders associated with pregnant females such as, for example,osteomalacia and preeclampsia and disorders associated with a fetus suchas, for example, neural tube defects and various fetal abnormalities.“Disease states” may comprise any pulmonary disorder such as, forexample, bronchitis, bronchiectasis, atelectasis, pneunomia, diseasescaused by inorganic dusts, diseases caused by organic dusts, anypulmonary fibrosis, and pleurisy. “Disease states” may comprise anyhematological/oncological disorder such as, for example, anemia,hemophilia, leukemia, and lymphoma. A “disease state” may comprise anycancer such as, for example, breast cancer, lung cancer, prostatecancer, pancreatic cancer, liver cancer, stomach cancer, testicularcancer, ovarian cancer, skin cancer, cancer of the brain, cancer of themouth, cancer of the throat, and cancer of the neck. “Disease states”may comprise any disorder of the immune system such as, for example,acquired immune deficiency syndrome (AIDS), AIDS-related complex,infection by any strain of any human immunodeficiency virus (HIV), andother viruses or pathogens such as bacteria, fungi and parasites. A“disease state” may comprise any cardiovascular disorder such as, forexample, arterial hypertension, orthostatic hypotension,arteriosclerosis, coronary artery disease, cardiomyopathy, anyarrhythmia, any valvular heart disease, endocarditis, pericardialdisease, any cardiac tumor, any aneurysm, and any peripheral vasculardisorder. “Disease states” may comprise any hepatic/biliary disordersuch as, for example, jaundice, hepatic steatosis, fibrosis, cirrhosis,hepatitis, any hepatic granuloma, any liver tumor, cholelithiasis,cholecystitis, and choledocholithiasis.

The term “physiologically stressful state,” as used herein, comprisesany state of an organism in which the organism faces one or morephysiological challenges. A “physiologically stressful state” maycomprise pregnancy, lactation, or conditions in which an organism facesphysiological challenges related to, for example, elevated metabolicdemand, increased plasma volume, or decreased concentrations ofnutrient-binding proteins. A “physiologically stressful state” mayresult from one or more disease states.

The term “subject,” as used herein, comprises any and all organisms andincludes the term “patient.” “Subject” may refer to a human or any otheranimal. “Subject” may also refer to a fetus.

The phrase “co-administration” refers to administration of twocompositions to a patient together or within a certain desired time.

The phrase “chewable form” refers to any relatively soft compositionsthat are chewed in the mouth after oral administration, have a pleasanttaste and mouthfeel, and quickly break into smaller pieces and begin todissolve after chewing such that they can be swallowed substantially asa solution.

The phrase “dissolvable form” refers to any compositions that dissolveinto a solution in the mouth. Such compositions, in one embodiment, maydissolve within about 60 seconds or less after placement in the mouthwithout any chewing.

The term “mouthfeel” refers to non-taste-related aspects of thepleasantness experienced by a person while chewing or swallowing anutritional supplement. Aspects of mouthfeel include, for example andwithout limitation, the hardness and brittleness of a composition,whether the composition is chewy, gritty, oily, creamy, watery, sticky,easily dissolved, astringent, effervescent, and the like, and the size,shape, and form of the composition (tablet, powder, gel, etc.).

The term “antioxidant” means an agent which inhibits oxidation and thusis used to prevent deterioration of preparations by the oxidativeprocess. Such compounds include, by way of example and withoutlimitation, ascorbic acid, ascorbyl palmitate, butylated hydroxyanisole,butylated hydroxytoluene, hypophophorous acid, monothioglycerol, propylgallate, sodium ascorbate, sodium bisulfite, sodium formaldehydesulfoxylate and sodium metabisulfite and others known to those ofordinary skill in the art.

The phrase “pharmaceutically acceptable,” as used herein, refers tothose compounds, materials, compositions and/or dosage forms which are,within the scope of sound medical judgment, suitable for use in contactwith the tissues of human beings and animals without excessive toxicity,irritation, allergic response, or other problem or complication,commensurate with a reasonable benefit/risk ratio. Thus, the phrase“pharmaceutically acceptable carriers,” as used herein, refers to suchsuitable compounds and materials defined above that may be added to thedosage form to assist in satisfactory processing of the dosage form orprovide desirable physical characteristics to the dosage form. Forexample, “pharmaceutically acceptable carriers” may include, but is notlimited to, binders, diluents, lubricants, glidants, colorants,emulsifiers, disintegrants, starches, water, oils, alcohols,preservatives, and sugars. In another example, “pharmaceuticallyacceptable carriers” refers to dosage forms such as gel-caps used with,for example, the compositions of the present invention comprising orconsisting of omega-3 fatty acids such as docosahexaenoic acid (DHA).Thus, “pharmaceutically acceptable carriers” in gel-caps may be in forexample, liquid or oil form, and may include a filler or otherappropriate liquid vehicle and may be used with omega-3 fatty acids suchas docosahexaenoic acid (DHA).

The phrase “swallowable form” refers to any compositions that do notreadily dissolve when placed in the mouth and may be swallowed wholewithout any chewing or discomfort. Such compositions, in one embodiment,may have a shape containing no sharp edges and a smooth, uniform andsubstantially bubble free outer coating.

The term “dosage form,” as used herein, is the form in which the dose isto be administered to the subject or patient. The drug or supplement isgenerally administered as part of a formulation that includes nonmedicalagents. The dosage form has unique physical and pharmaceuticalcharacteristics. Dosage forms may be solid, liquid or gaseous. Solidforms include, but are not limited to pills, capsules, tablets, gelcaplets, softgels, lozenges, wafers etc.

The term “substantially free of added” as used herein, means free fromtherapeutically effective amounts of compounds when administered insuggested doses, but may include trace amounts of compounds innon-therapeutically effective amounts. For example, a composition of thepresent invention that included an inactive ingredient that is a salt orcompound including a mineral would still be substantially free of addedminerals.

As used herein, the terms “inactive,” “inert,” “excipient,” and/or“formulatory” refer to any compound that is an inactive ingredient of adescribed composition. The definition of “inactive ingredient” as usedherein follows that of the U.S. Food and Drug Administration, as definedin 21 C.F.R. 201.3(b)(8), which is any component of a drug product otherthan the active ingredient.

By “active ingredient,” then, is meant any compound intended to furnishpharmacological activity or other direct effect in the diagnosis, cure,mitigation, treatment and/or prevention of a condition. See 21 C.F.R.210.3(b)(7). Further, “active ingredients” include those compounds ofthe composition that may undergo chemical change during the manufactureof the composition and be present in the final composition in a modifiedform intended to furnish an activity or effect. Id.

The term “administrable” defines a composition that is able to be givento a patient. Likewise, “administering” refers to the act of giving acomposition to a patient or otherwise making such composition availableto a patient or the patient taking a composition.

As used herein, the term “about,” when located before a dosage amount ordosage range of a specific ingredient, refers to an amount or rangeclosely above and/or closely below the stated amount or range that doesnot manifestly alter the therapeutic effect of the specific ingredientfrom the stated amount or range.

Proper nutrition is essential for maintaining health and preventingdiseases. Adequate nutrition is especially critical during, for example,nutritionally volatile or physiologically stressful periods such asthose including, by way of example and without limitation, pregnancy,lactation, or any disease state. Vitamin and mineral needs are almostuniversally increased throughout these periods. Increased needs duringphysiologically stressful states such as pregnancy, lactation or diseasestate may result from elevated metabolic demand, increased plasmavolume, increased quantities of circulating red blood cells, decreasedconcentrations of nutrients, and decreased concentrations ofnutrient-binding proteins such as, for example and without limitation,serum-ferritin, maltose-binding protein, lactoferrin, calmodulin,tocopheryl binding protein, riboflavin binding protein, retinol bindingprotein, transthyretin, high density lipoprotein-apolipoprotein A1,folic acid binding protein, and 25-hydroxyvitamin D binding protein.Lapido, 72 (Supp.) AMER. J. CLIN. NUTR. 280S-90S (2000).

Optimizing specific nutrients before, during, and after thephysiological processes of pregnancy and lactation can have profound,positive, and comprehensive impacts on the overall wellness of thedeveloping and newborn child as well as on the safety and health of themother. Black, 85 (Supp.) BRIT. J. NUTR. S193-97 (2001); Scholl et al.,146 AMER. J. EPIDEM. 134-41 (1997). Nutrients provided to a mother reachthe fetus. Specifically, it is established that substrates for growthand development, for example, circulate within the same pathways thatcarry drugs to and waste products from the fetus. Exchanges of materialbetween mother and fetus occur primarily in the placenta, where villicontaining fetal capillaries protrude into sinuses (intervillousspaces). Maternal arterial blood spurts into these spaces, then drainsinto maternal uterine veins to be returned to the maternal systemiccirculation. Solutes in maternal blood cross the epithelial cells andconnective tissue of the villi and the endothelium of the fetalcapillaries; these solutes are then carried to the fetus by placentalveins, which converge into the umbilical vein. THE MERCK MANUAL OFDIAGNOSIS AND THERAPY 2022 (Mark H. Beers, M.D. & Robert Berkow, M.D.,eds., 17th ed. 1999).

The kits and methods of the present invention provide the means tooptimize good health by utilizing vitamin and mineral nutritionalsupplementation. The kits and methods of the present invention may beadministered to or directed to a subject such as a human or any otherorganism.

The compositions of the kits and methods of the present invention mayinclude vitamin A. Vitamin A is involved in physiological processes thatresult in cellular differentiation, cellular maturity, and cellularspecificity. Thus, vitamin A is an important component of a nutritionalsupplement for subjects in physiologically stressful states, such asthose caused by pregnancy, lactation or disease state. Zile et al.,131(3) J. NUTR. 705-08 (2001). Care should be taken, however, to avoidexcess. Indeed, supplemental vitamin A ingestion during pregnancy hasbeen shown in some studies to be teratogenic or deforming to human andanimal embryos. G B Mulder et al., 62(4) TERATOLOGY 214-26 (2000). Thus,in a specific embodiment of the invention, vitamin A may be included inamounts ranging from about 550 IU to about 1650 IU. In another specificembodiment, vitamin A may be included in amounts ranging from about 880IU to about 1320 IU. In another specific embodiment, vitamin A may beincluded in amounts ranging from about 990 IU to about 1210 IU. Inanother embodiment, vitamin A may be included in an amount of about 1100IU.

In a specific embodiment of the present invention, vitamin A may beincluded in the form of acetate. In another specific embodiment, vitaminA in the form of acetate may be included in amounts ranging from about550 IU to about 1650 IU. In another specific embodiment, vitamin A inthe form of acetate may be included in amounts ranging from about 880 IUto about 1320 IU. In another specific embodiment, vitamin A in the formof acetate may be included in amounts ranging from about 990 IU to about1210 IU. In another embodiment, vitamin A in the form of acetate may beincluded in an amount of about 1100 IU.

The compositions of the kits and methods of the present invention mayinclude beta carotene. Beta carotene is converted to vitamin A withinthe body as needed. Mayne, 10 J. FASEB 690-701 (1996). Beta carotenealso has powerful anti-oxidant properties. Antioxidants are importantduring physiologically stressful events for numerous reasons. Forexample, lipid peroxidation has been associated with over 200 diseaseprocesses. Rock et al., 96(7) J. AMER. DIET. ASSOC. 693-702 (1996).Antioxidants are especially important during pregnancy because in thefirst trimester, establishment of blood flow into the intervillous spaceis associated with a burst of oxidative stress. The inability to mountan effective antioxidant defense against this burst results in earlypregnancy loss. Myatt & Cui, 122, HISTOCHEM. CELL BIOL., 369-82 (2004).Further, oxidative stress has been implicated in the pathophysiology ofpreeclampsia, a toxemia of pregnancy. Llurba et al., 37(4) FREE RADIC.BIOL. MED. 557-70 (2004). Finally, oxidative stress during pregnancyplays an important role in fetal growth, and healthy antioxidant levelsare positively correlated with birth weight and length. Myatt & Cui; Leeet al., 58 EUR. J. CLIN. NUTR., 481-87 (2004).

In a specific embodiment of the present invention, beta carotene may beincluded in amounts ranging from about 300 IU to about 900 IU. Inanother specific embodiment of the present invention, beta carotene maybe included in amounts ranging from about 480 IU to 720 IU. In anotherspecific embodiment of the present invention, beta carotene may beincluded in amounts ranging from about 540 IU to about 660 IU. Inanother embodiment, beta carotene may be included in an amount of about600 IU.

The compositions of the kits and methods of the present invention maycomprise or use B-complex vitamins. This class of vitamins compriseswater-soluble nutrients generally not stored in the body. They playroles in a variety of biological processes critical to the health ofpregnant women, lactating women, and fetuses such as, for example, themetabolism of homocysteine. The B-complex vitamins that may be includedin the kits and methods of the present invention comprise one or more ofvitamin B₁, vitamin B₂, vitamin B₃, vitamin B₆, vitamin B₉ and vitaminB₁₂.

The compositions of the kits and methods of the present invention maycomprise or use vitamin B₁. Vitamin B₁ plays a role in carbohydratemetabolism and neural function. It is a coenzyme for the oxidativedecarboxylation of alpha-ketoacids (e.g., alpha-ketoglutarate andpyruvate) and for transketolase, which is a component of the pentosephosphate pathway. NATIONAL RESEARCH COUNCIL, RECOMMENDED DIETARYALLOWANCES 123 (10th ed. 1989) (hereinafter “RDA”). In a specificembodiment of the present invention, vitamin B₁ may be included in theform of thiamine mononitrate. In another specific embodiment, vitamin B₁may be included in amounts ranging from about 1.0 mg to about 3.0 mg. Inanother specific embodiment, vitamin B₁ may be included in amountsranging from about 1.3 mg to about 1.9 mg. In another specificembodiment, vitamin B₁ may be included in amounts ranging from about 1.5mg to about 1.75 mg. In another embodiment, vitamin B₁ may be includedin an amount of about 1.6 mg.

In another specific embodiment, vitamin B₁ in the form of thiaminemononitrate may be included in amounts ranging from about 1.0 mg toabout 3.0 mg. In another specific embodiment, vitamin B₁ in the form ofthiamine mononitrate may be included in amounts ranging from about 1.3mg to about 1.9 mg. In another specific embodiment, vitamin B₁ in theform of thiamine mononitrate may be included in amounts ranging fromabout 1.5 mg to about 1.75 mg. In another embodiment, vitamin B₁ in theform of thiamine mononitrate may be included in an amount of about 1.6mg.

The compositions of the kits and methods of the present invention maycomprise or use vitamin B₂. Vitamin B₂ is a component of two flavincoenzymes, flavin mononucleotide (FMN) and flavin adenine dinucleotide(FAD). These flavoenzymes are involved in a number ofoxidation-reduction reactions including the conversion of pyridoxine andniacin. RDA, supra at 132. Flavoenzymes also play a role in a number ofmetabolic pathways such as amino acid deamination, purine degradationand fatty acid oxidation and thus help to maintain carbohydrate, aminoacid and lipid metabolism. In a specific embodiment of the presentinvention, vitamin B₂ may be included in the form of riboflavin. Inanother specific embodiment, vitamin B₂ may be included in amountsranging from about 1 mg to about 3 mg. In another specific embodiment,vitamin B₂ may be included in amounts ranging from about 1.5 mg to about2.2 mg. In another specific embodiment, vitamin B₂ may be included inamounts ranging from about 1.6 mg to about 2 mg. In another embodiment,vitamin B₂ may be included in an amount of about 1.8 mg.

In another specific embodiment, vitamin B₂ in the form of riboflavin maybe included in amounts ranging from about 1 mg to about 3 mg. In anotherspecific embodiment, vitamin B₂ in the form of riboflavin may beincluded in amounts ranging from about 1.5 mg to about 2.2 mg. Inanother specific embodiment, vitamin B₂ in the form of riboflavin may beincluded in amounts ranging from about 1.6 mg to about 2 mg. In anotherembodiment, vitamin B₂ in the form of riboflavin may be included in anamount of about 1.8 mg.

The compositions of the kits and methods of the present invention maycomprise or use vitamin B₃. Vitamin B₃, or “niacin” is the common namefor two compounds: nicotinic acid (also called niacin) and niacinamide(also called nicotinamide). Vitamin B₃ is particularly important formaintaining healthy levels and types of fatty acids. It is also requiredfor the synthesis of pyroxidine, riboflavin, and folic acid. RDA, supraat 137. Administration of vitamin B₃ also may effect a reduction intotal cholesterol (LDL) and very low density lipoprotein (VLDL) levelsand an increase in high density lipoprotein (HDL) cholesterol levels.Nicotinamide adenine dinucleotide (NAD) and NAD phosphate (NADP) areactive coenzymes of niacin. These coenzymes are involved in numerousenzymatic reactions such as glycolysis, fatty acid metabolism, andsteroid synthesis. Henkin et al., 91 AM. J. MED. 239-46 (1991). In aspecific embodiment of the present invention, vitamin B₃ may be includedin the form of niacinamide. In another specific embodiment, the presentinvention may include an equivalent molar amount of niacin. In anotherspecific embodiment, vitamin B₃ may be included in amounts ranging fromabout 7 mg to about 23 mg. In another specific embodiment, vitamin B₃may be included in amounts ranging from about 12 mg to about 18 mg. Inanother specific embodiment, vitamin B₃ may be included in amountsranging from about 13.5 mg to about 16.5 mg. In another embodiment,vitamin B₃ may be included in an amount of about 15 mg.

In another specific embodiment, vitamin B₃ in the form of niacinamidemay be included in amounts ranging from about 7 mg to about 23 mg. Inanother specific embodiment, vitamin B₃ in the form of niacinamide maybe included in amounts ranging from about 12 mg to about 18 mg. Inanother specific embodiment, vitamin B₃ in the form of niacinamide maybe included in amounts ranging from about 13.5 mg to about 16.5 mg. Inanother embodiment, vitamin B₃ in the form of niacinamide may beincluded in an amount of about 15 mg.

The compositions of the kits and methods of the present invention maycomprise or use vitamin B₆. The administration of vitamin B₆ may reducethe levels of homocysteine. Bostom et al., 49 KIDNEY INT. 147-52 (1996).The active forms of vitamin B₆, pyridoxal-5′-phosphate (PLP) andpyridoxamine-5′-phosphate, are coenzymes for numerous enzymes and assuch, are important for gluconeogenesis, niacin formation, anderythrocyte metabolism. RDA, supra at 142-43. Vitamin B₆ is a coenzymefor both cystathionine synthase and cystathionase, enzymes that catalyzethe formation of cysteine from methionine. Homocysteine is anintermediate in this process and elevated levels of plasma homocysteineare recognized as a risk factor for both vascular disease (Robinson etal., 94 CIRCULATION 2743-48 (1996)) and neural tube defects (Locksmith &Duff, 91 OBSTET. GYNECOL. 1027-34 (1998)). In a specific embodiment ofthe present invention, vitamin B₆ may be included in the form ofpyridoxine hydrochloride. In another specific embodiment, vitamin B₆ maybe included in amounts ranging from about 1 mg to about 4 mg. In anotherspecific embodiment, vitamin B₆ may be included in amounts ranging fromabout 2 mg to about 3 mg. In another specific embodiment, vitamin B₆ maybe included in amounts ranging from about 2.3 mg to about 2.8 mg. Inanother embodiment, vitamin B₆ may be included in an amount of about 2.5mg.

In another specific embodiment, vitamin B₆ in the form of pyridoxinehydrochloride may be included in amounts ranging from about 1 mg toabout 4 mg. In another specific embodiment, vitamin B₆ in the form ofpyridoxine hydrochloride may be included in amounts ranging from about 2mg to about 3 mg. In another specific embodiment, vitamin B₆ in the formof pyridoxine hydrochloride may be included in amounts ranging fromabout 2.3 mg to about 2.8 mg. In another embodiment, vitamin B₆ in theform of pyridoxine hydrochloride may be included in an amount of about2.5 mg.

The compositions of the kits and methods of the present invention maycomprise or use vitamin B₉. This vitamin has demonstrated the ability toprevent neural tube defects such as spina bifida caused by disturbedhomocysteine metabolism. Vanderput et al., EXP. BIOL. MED. 243-70(2001); DeFalco et al., 27 CLIN. EXP. OBSTET. GYNECOL. 188-90 (2000);Eskes, 27 CLIN. EXP. OBSTET. GYNECOL. 157-67 (2000); Locksmith & Duff,supra. Vitamin B₉ also is important for the formation of red and whiteblood cells within bone marrow and plays a role in heme formation.Further, folate deficiencies inhibit the activity of vitamin B₁. RDA,supra at 150. In a specific embodiment of the present invention, vitaminB₉ may be included in the form of folic acid. In another embodiment,vitamin B₉ may be included in the forms of folic acid, folacin,metafolin, folate and/or one or more natural isomers of folate including(6S)-tetrahydrofolic acid or a polyglutamyl derivative thereof,5-methyl-(6S)-tetrahydrofolic acid or a polyglutamyl derivative thereof,5-formyl-(6S)-tetrahydrofolic acid or a polyglutamyl derivative thereof,10-formyl-(6R)-tetrahydrofolic acid or a polyglutamyl derivativethereof, 5,10-methylene-(6R)-tetrahydrofolic acid or a polyglutamylderivative thereof, 5,10-methenyl-(6R)-tetrahydrofolic acid or apolyglutamyl derivative thereof and 5-formimino-(6S)-tetrahydrofolicacid or a polyglutamyl derivative thereof. In a specific embodiment,vitamin B₉ may be in the form of pteroylglutamic acid. In anotherspecific embodiment, vitamin B₉ may be included in amounts ranging fromabout 500 μg to about 1500 μg. In another specific embodiment, vitaminB₉ may be included in amounts ranging from about 800 μg to about 1200μg. In another specific embodiment, vitamin B₉ may be included inamounts ranging from about 900 μg to about 1100 μg. In anotherembodiment, vitamin B₉ may be included in an amount of about 1000 μg.

In another specific embodiment, vitamin B₉ in the form of folic acid maybe included in amounts ranging from about 500 μg to about 1500 μg. Inanother specific embodiment, vitamin B₉ in the form of folic acid may beincluded in amounts ranging from about 800 μg to about 1200 μg. Inanother specific embodiment, vitamin B₉ in the form of folic acid may beincluded in amounts ranging from about 900 μg to about 1100 μg. Inanother embodiment, vitamin B₉ in the form of folic acid may be includedin an amount of about 1000 μg.

The compositions of the kits and methods of the present invention maycomprise or use vitamin B₁₂. Vitamin B₁₂ can be converted to the activecoenzymes, methylcobalamin and 5′-deoxyadenosylcobalamin. Thesecoenzymes are necessary for folic acid metabolism, conversion ofcoenzyme A and myelin synthesis. Methylcobalamin also catalyzes thedemethylation of a folate cofactor which is involved in DNA synthesis. Alack of demethylation may result in folic acid deficiency. RDA, supra at159-160. Deoxyadenosylcobalamin is the coenzyme for the conversion ofmethylmalonyl-CoA to succinyl-CoA, which plays a role in the citric acidcycle. Cobalamin, along with pyridoxine and folic acid, also areimplicated in the proper metabolism of homocysteine, a breakdown productof the amino acid methionine, which is correlated with an increased riskof heart disease due to its negative effects on endothelial function. Inone specific embodiment of the present invention, vitamin B₁₂ may beincluded in the form of cyanocobalamin. In another specific embodiment,vitamin B₁₂ may be included in amounts ranging from about 2 μg to about8 μg. In another specific embodiment, vitamin B₁₂ may be included inamounts ranging from about 4 μg to about 6 μg. In another specificembodiment, vitamin B₁₂ may be included in amounts ranging from about4.5 μg to about 5.5 μg. In another embodiment, vitamin B₁₂ may beincluded in an amount of about 5 μg.

In another specific embodiment, vitamin B₁₂ in the form ofcyanocobalamin may be included in amounts ranging from about 2 μg toabout 8 μg. In another specific embodiment, vitamin B₁₂ in the form ofcyanocobalamin may be included in amounts ranging from about 4 μg toabout 6 μg. In another specific embodiment, vitamin B₁₂ in the form ofcyanocobalamin may be included in amounts ranging from about 4.5 μg toabout 5.5 μg. In another embodiment, vitamin B₁₂ in the form ofcyanocobalamin may be included in an amount of about 5 μg.

The compositions of the kits and methods of the present invention maycomprise or use vitamin C. The major biochemical role of water-solublevitamin C is as a co-substrate in metal catalyzed hydroxylations. Likebeta carotene, vitamin C has antioxidant properties. It interactsdirectly with superoxide hydroxyl radicals and singlet oxygen, and alsoprovides antioxidant protection for folate and vitamin E, keepingvitamin E in its most potent form. Vitamin C may afford protectiveeffects against preeclampsia by participating in the scavenging of freeradicals. Indeed, significantly lower levels of vitamin C have beenobserved in preeclamptic women than in controls. Woods et al., 185(1)AM. J. OBSTET. GYNECOL. 5-10 (2001); Kharb, 1 EURO. J. OBSTET. GYNECOL.REPROD. BIOL. 37-39 (2000); Milczarek et al., 210 MOL. CELL BIOCHEM.65-73 (2000). Vitamin C also enhances the absorption of iron. RDA, supraat 115. In addition, vitamin C is required for collagen synthesis,epinephrine synthesis, and bile acid formation. Moreover, vitamin C hasbeen implicated in inhibiting atherosclerosis by being present inextracellular fluid of the arterial wall and potentiating nitric oxideactivity, thus normalizing vascular function. In a specific embodimentof the present invention, vitamin C may be included in the form ofascorbic acid. In another specific embodiment, vitamin C may be includedin amounts ranging from about 30 mg to about 90 mg. In another specificembodiment, vitamin C may be included in amounts ranging from about 48mg to about 72 mg. In another specific embodiment, vitamin C may beincluded in amounts ranging from about 54 mg to about 66 mg. In anotherembodiment, vitamin C may be included in an amount of about 60 mg.

In another specific embodiment, vitamin C in the form of ascorbic acidmay be included in amounts ranging from about 30 mg to about 90 mg. Inanother specific embodiment, vitamin C in the form of ascorbic acid maybe included in amounts ranging from about 48 mg to about 72 mg. Inanother specific embodiment, vitamin C in the form of ascorbic acid maybe included in amounts ranging from about 54 mg to about 66 mg. Inanother embodiment, vitamin C in the form of ascorbic acid may beincluded in an amount of about 60 mg.

The compositions of the kits and methods of the present invention maycomprise or use vitamin D₃. Vitamin D₃ is a fat-soluble “hormone like”substance important for the maintenance of healthy bones. This vitaminincreases the absorption of calcium and phosphorous from thegastrointestinal tract, and improves mineral resorption into bonetissue. Vitamin D can be converted to its active form from exposure ofthe skin to sunlight. This fact is among the reasons why vitamin Ddeficiency is common in the elderly, notably the institutionalized, whospend little or no time out of doors. Deficiencies in vitamin D₃ canlead to increased bone turnover and loss, and when severe, osteomalacia,or softening of the bones. Supplementation with vitamin D₃ has beenshown to moderately reduce bone loss, increase serum 25-hydroxyvitaminD, and decrease serum parathyroid hormone levels. Dawson-Hughes et al.,337 NEW ENG. J. MED. 670-76 (1997); Lips et al., 86 J. CLIN. ENDOCRINOL.METAS. 1212-21 (2001). Vitamin D₃ also plays a role in the maintenanceof calcium and phosphorus homeostasis, but it is also active in celldifferentiation and immune function. In a specific embodiment of thepresent invention, vitamin D₃ may be included in the form ofcholecalciferol. In another specific embodiment, vitamin D₃ may beincluded in amounts ranging from about 200 IU to about 600 IU. Inanother specific embodiment, vitamin D₃ may be included in amountsranging from about 320 IU to about 480 IU. In another specificembodiment, vitamin D₃ may be included in amounts ranging from about 360IU to about 440 IU. In another embodiment, vitamin D₃ may be included inan amount of about 400 IU.

In another specific embodiment, vitamin D₃ in the form ofcholecalciferol may be included in amounts ranging from about 200 IU toabout 600 IU. In another specific embodiment, vitamin D₃ in the form ofcholecalciferol may be included in amounts ranging from about 320 IU toabout 480 IU. In another specific embodiment, vitamin D₃ in the form ofcholecalciferol may be included in amounts ranging from about 360 IU toabout 440 IU. In another embodiment, vitamin D₃ in the form ofcholecalciferol may be included in an amount of about 400 IU.

The compositions of the kits and methods of the present invention maycomprise or use vitamin E. Vitamin E is a fat-soluble vitaminantioxidant found in biological membranes where it protects thephospholipid membrane from oxidative stress. Vitamin E inhibits theoxidation of unsaturated fatty acids by trapping peroxyl free radicals.It is also an antiatherogenic agent, and studies have demonstrated areduced risk of coronary heart disease with increased intake of vitaminE. Stampfer et al., 328 NEW ENG. J. MED. 1444-49 (1993). In addition,vitamin E, like beta carotene and vitamin C, may afford protectiveeffects against preeclampsia by participating in the scavenging of freeradicals. As with vitamin C, significantly lower levels of vitamin Ehave been observed in preeclamptic women than in controls. Woods et al.,supra; Kharb, supra; Milczarek et al., supra. In a specific embodimentof the present invention, vitamin E may be included in the form ofd-alpha-tocopheryl acetate. In another specific embodiment, vitamin Emay be included in the form of an equivalent molar amount of d-alphatocopheryl succinate. In another specific embodiment, vitamin E may beincluded in amounts ranging from about 15 IU to about 45 IU. In anotherspecific embodiment, vitamin E may be included in amounts ranging fromabout 24 IU to about 36 IU. In another specific embodiment, vitamin Emay be included in amounts ranging from about 27 IU to about 33 IU. Inanother embodiment, vitamin E may be included in an amount of about 30IU.

In another specific embodiment, vitamin E in the form ofd-alpha-tocopheryl acetate may be included in amounts ranging from about15 IU to about 45 IU. In another specific embodiment, vitamin E in theform of d-alpha-tocopheryl acetate may be included in amounts rangingfrom about 24 IU to about 36 IU. In another specific embodiment, vitaminE in the form of d-alpha-tocopheryl acetate may be included in amountsranging from about 27 IU to about 33 IU. In another embodiment, vitaminE in the form of d-alpha-tocopheryl acetate may be included in an amountof about 30 IU.

The compositions of the kits and methods of the present invention maycomprise or use iron. A primary function of iron is to carry oxygen tobodily tissues via the hemoglobin part of red blood cells. Supplementalintake of iron is critical to preventing anemia, a disorder associatedwith a variety of physiological states including, for example,pregnancy. Bothwell, 72(Supp.) AM. J. CLIN. NUTR. 257S-64S (2000).Severe anemia may have adverse effects upon a mother and a fetus.Specifically, significant depression of hemoglobin has been associatedwith poor pregnancy outcome. Black, supra; Sifakis & Pharmakides, 900ANN. N.Y. ACAD. SCI. 125-36 (2000). The kits and methods of the presentinvention may include iron in either chelated or nonchelated form. In aspecific embodiment of the present invention, iron may be included inthe form of polysaccharide iron complex. In another specific embodiment,iron may be included in the form of an equivalent molar amount offerrous fumurate. For women in developed countries, however, who aregenerally clinically healthy and have access to adequate nutrition, thebenefits of excessive iron supplementation are unclear, and there may berisks. B W Graves at al., J MIDWIFERY WOMENS HEALTH, 2001 May-June;46(3):159-66 Thus, a “conservative” approach may be a lowersupplementation of iron than currently available. Thus, in a specificembodiment of the present invention, iron may be included in amountsranging from about 14 mg to about 44 mg. In another specific embodiment,iron may be included in amounts ranging from about 23 mg to about 35 mg.In another specific embodiment, iron may be included in amounts rangingfrom about 26 mg to about 32 mg. In another embodiment, iron may beincluded in an amount of about 29 mg.

In another specific embodiment, iron in the form of polysaccharide ironcomplex may be included in amounts ranging from about 14 mg to about 44mg. In another specific embodiment, iron in the form of polysaccharideiron complex may be included in amounts ranging from about 23 mg toabout 35 mg. In another specific embodiment, iron in the form ofpolysaccharide iron complex may be included in amounts ranging fromabout 26 mg to about 32 mg. In another embodiment, iron in the form ofpolysaccharide iron complex may be included in an amount of about 29 mg.

The compositions of the kits and methods of the present invention maycomprise or use magnesium. Magnesium is found primarily in both bone andmuscle and is important for over 300 different enzyme reactions. Aprimary function of magnesium is to bind to phosphate groups inadenosine triphosphate (ATP), thereby forming a complex that assists inthe transfer of ATP phosphate. Magnesium also functions within cells asa membrane stabilizer. Magnesium plays roles in nucleic acid synthesis,glycolysis, transcription of DNA and RNA, amino acid activation,membrane transport, transketolase reactions, and protein synthesis.James L. L. Groff et al., ADVANCED NUTRITION AND HUMAN METABOLISM 341(2d ed. 1996). It is also involved in the formation of cAMP, a cytosolicsecond messenger that plays a role in cell signaling mechanisms.Magnesium also functions both synergistically and antagonistically withcalcium in neuromuscular transmission. RDA, supra at 188. Specifically,magnesium is critical for the maintenance of electrochemical potentialsof nerve and muscle membranes and the neuromuscular junctiontransmissions, particularly important in the heart. Not surprisingly,magnesium deficiency is tied to cardiovascular disease and hypertension.Agus et al., 17 CRIT. CARE CLIN. 175-87 (2001). Indeed, oral magnesiumtherapy improves endothelial function in patients with coronary disease.Shechter et al., 102 CIRCULATION 2353-58 (2000).

Magnesium is available in a variety of salts and can be included in thekits and methods of the present invention in either chelated ornonchelated form. In one specific embodiment of the present invention,magnesium may be included in the form of magnesium oxide. In anotherspecific embodiment, magnesium may be included in amounts ranging fromabout 12 mg to about 38 mg. In another specific embodiment, magnesiummay be included in amounts ranging from about 20 mg to about 30 mg. Inanother specific embodiment, magnesium may be included in amountsranging from about 22.5 mg to about 27.5 mg. In another embodiment,magnesium may be included in an amount of about 25 mg.

In another specific embodiment, magnesium in the form of magnesium oxidemay be included in amounts ranging from about 12 mg to about 38 mg. Inanother specific embodiment, magnesium in the form of magnesium oxidemay be included in amounts ranging from about 20 mg to about 30 mg. Inanother specific embodiment, magnesium in the form of magnesium oxidemay be included in amounts ranging from about 22.5 mg to about 27.5 mg.In another embodiment, magnesium in the form of magnesium oxide may beincluded in an amount of about 25 mg.

The compositions of the kits and methods of the present invention maycomprise or use zinc. Zinc plays a role in numerous metabolic activitiessuch as nucleic acid production, protein synthesis, and development ofthe immune system. There are more than 200 zinc metalloenzymes includingaldolase, alcohol dehydrogenase, RNA polymerase, and protein kinase C.Zima et al., 17 BLOOD PURIF. 182-86 (1999). Zinc stabilizes RNA and DNAstructures, forms zinc fingers in nuclear receptors, and is a componentof chromatin proteins involved in transcription and replication.Deficiencies of zinc during pregnancy have been shown to contribute tosevere fetal abnormalities. Srinivas et al., 68(6) INDIAN J. PEDIATR.519-22 (2001); Yang et al., 13(4) BIOMED. ENVIRON. SCI. 280-86 (2000);King, 71(Supp.) AM. J. CLIN. NUTR. 1334S-43S (2000). Indeed, therecommended daily allowance for zinc increases during pregnancy. Ahigher dose of zinc, however, is associated with causing nausea in somepatients. Thus, for pregnant women or other patients that are moresusceptible to nausea, a conservative amount of zinc that still providesadequate nutritional supplementation is desirable. In another specificembodiment, zinc may be included in amounts ranging from about 7 mg toabout 23 mg. In another specific embodiment, zinc may be included inamounts ranging from about 12 mg to about 18 mg. In another specificembodiment, zinc may be included in amounts ranging from about 13.5 mgto about 16.5 mg. In another embodiment, zinc may be included in anamount of about 15 mg.

Zinc is available in many forms and may be included in the kits andmethods of the present invention in chelated or nonchelated form. In aspecific embodiment of the present invention, zinc may be included inthe form of zinc oxide. In another specific embodiment, zinc in the formof zinc oxide may be included in amounts ranging from about 7 mg toabout 23 mg. In another specific embodiment, zinc in the form of zincoxide may be included in amounts ranging from about 12 mg to about 18mg. In another specific embodiment, zinc in the form of zinc oxide maybe included in amounts ranging from about 13.5 mg to about 16.5 mg. Inanother embodiment, zinc in the form of zinc oxide may be included in anamount of about 15 mg.

The compositions of the kits and methods of the present invention maycomprise or use omega-3 fatty acids. Omega-3 fatty acids play integralroles in physiological mechanisms that serve to prevent, treat and/oralleviate the occurrence or negative effects of some diseases and hasshown multiple health-promoting properties in adults. For example,omega-3 fatty acids are linked to health benefits such as preventing theoccurrence of cancer, preventing the occurrence of heart disease, andare helpful in brain health and immune function. Indeed, omega-3 fattyacids include essential fatty acids linked to numerous health benefits,such as docahexaenoic acid (or docosahexaenoic acid, DHA),eicosapentaenoic acid (EPA) and α-linolenic acid (ALA). In anotherspecific embodiment, the kits and methods of the present invention maycomprise or use Docahexaenoic acid (or docosahexaenoic acid, DHA). Inanother specific embodiment, the kits and methods of the presentinvention may comprise or use eicosapentaenoic acid (EPA). In anotherspecific embodiment, the kits and methods of the present invention maycomprise or use α-linolenic acid (ALA).

The omega-3 fatty acid DHA, a major component of fish oil, has beenshown to be of particular importance, especially during pregnancy or forlowering blood pressure. Indeed, studies suggest that DHA, but not EPA,reduce ambulatory blood pressure and heart rate in hyperlipidemic men. TA Mori et al., HYPERTENSION. 34:253-260 (1999). The results of thisstudy thus suggest that DHA is the principal fatty acid in fish and fishoils that is responsible for blood pressure and heart rate effects inhumans. Id.

Further, DHA is vital for optimal fetal and infant brain/cognitivedevelopment, as well as for normal brain function throughout life. F MRioux, O. Hernell et al., ACTA PAEDIATR 95(2):137-144 (2006). The sleeppatterns of infants born to mothers with higher plasma phospholipid DHAsuggest greater central nerve system maturity. S R Cheruku, C JLammi-Keefe et al., AM J CLIN NUTR 76:608-613, 2002. Additionally,children with Attention Deficit Hyperactivity Disorder (ADHD) have beenshown to have abnormal levels of DHA. E A Mitchell, M. Manku et al.,CLIN PEDIATR 26:406-411 (1986); L J Stevens, J R Burgess et al., PHYSIOLBEHAV 59:915-920 (1996). Studies have indicated a correlation betweenmaternal DHA intake and intelligence quotient in the child. The directcorrelation between brain development and systemic DHA status issecondary to the fact that DHA is taken up by the brain in preference toother fatty acids. Adequate DHA levels in pregnancy have also beencorrelated with optimizing the length of gestation and decreasing therisk of neurodevelopmental psychopathology. These critical findings haveprompted the National Institute of Health (NIH) to recommend thatpregnant women consume at least 300 mg of omega-3 fatty acids duringpregnancy. N. Neurenger et al., NUTR REV 44:285-294 (1986); G. Hornstraet al., AM J CLIN NUTR 71:285S-291S (2000); I B Helland et al.,PEDIATRICS 111:E39-E44 (2003); F. Facchinetti et al., EUR REV MEDPHARMACOL SCI 9(1):41-48 (2005); R K McNamara et al., PROSTAGLANDINSLEUKOT ESSENT FATTY ACIDS (29 Aug. 2006).

DHA is also important for the development of the infant retina andimproving the visual acuity of the infant. C A Francois, W E Connor etal., AM J CLIN NUTR 77:226-233 (2003). Preterm infants have a more rapiddevelopment of visual acuity if fed human milk or formula enriched withDHA, compared to standard formula. M H Jorgensen, K F Michaelsen et al.,LIPIDS 31(1):99-105 (1996). An increase in visual acuity has also beenobserved to develop more rapidly in term infants breast-fed from motherswhose diets are supplemented with DHA. Id.

In addition to the aforementioned benefit of DHA to the developingchild, this essential fatty acid has also shown multiplehealth-promoting properties in adults. These include anti-thrombotic,anti-inflammatory and anti-atherosclerotic activity, all of which reducethe risk of heart disease. M Laidlaw and B J Holub, AM J CLIN NUTR77:37-42 (2003). Inverse relationships have also been found betweensystemic levels of omega-3 fatty acids such as DHA and incidence andseverity of mood disorders and depression, including postpartumdepression. Therefore, introduction of omega-3 during pregnancy has adouble benefit, to both child and mother. F B Hu et al., JAMA287(14):1815-1821 (2002); C. Von Schacky et al., ANN INTERN MED130:554-562 (1999); G. Parker et al., AM J PSYCHIATRY 163(6):969-978(2006); S J Otto et al., PROSTAGLANDINS LEUKOT ESSENT FATTY ACIDS69(3):237-243 (2003).

For women, DHA is particularly useful in counteracting the progressionof breast cancer. Human breast cancer cells exposed to DHA exhibit anincrease in cell death by apoptosis. B A Stoll, BR J NUTR 87(3):193-198,2002. DHA also inhibits cyclooxygenase-2, which promotes mammarycarcinogenesis. Id. DHA supplementation during pregnancy has also beenshown to increase the length of gestation by about six days, helpingmothers carry to a healthy full term. C M Smuts et al., OBSTETRICS ANDGYNECOLOGY 101(3):469-479 (2003).

Intake of omega-3 fatty acids such as DHA not only leads to theirincorporation into cell membrane lipids (B A Stoll, BR J NUTR87(3):193-198 (2002)), but also storage in adipose tissue and secretionin breast milk. C A Francois, W E Connor et al., AM J CLIN NUTR77:226-233 (2003). Although the human body can derive a limited amountof DHA from another fatty acid known as alpha-linolenic acid, thisprocess is inefficient for optimal needs. A rich dietary source ofdirect DHA is fish. Id. However, some lactating women are vegetarians,have limited access to fish or simply do not like fish. A furtherproblem with encouraging increased fish intake in pregnancy is that mostspecies contain methyl mercury (MeHg) in various amounts. MeHg is apotent neurotoxin that can increase the risk of retarded cognitivedevelopment. This concern prompted both the United States EnvironmentalProtection Agency (2004) and the Food and Drug Administration (2001) toissue advisories recommending that pregnant women modify their fishconsumption. These recommendations have resulted in a reduced intake offish during pregnancy, thus helping to protect against fetal MeHgrelated harm. However, this has concurrently reduced maternal intake ofDHA. In fact, a recent dietary study of over 100 pregnant or nursingwomen in the United States showed an astonishingly low intake of DHA onaverage (60-80 mg/day), and a dangerously low percentage (<2) consumedthe aforementioned recommended intake of 300 mg/day of DHA as set forthby the NIH. JT Cohen et al., AM J PREV MED, 29:353-365 (2005); U.S.Department of Health and Human Services, U.S. Environmental ProtectionAgency, “What you need to know about mercury in fish and shellfish,”Report EPA-823-F-04-009 (March 2004); E. Oken et al., OBSTET GYNECOL102:346-351 (2003).

In these cases, nutritional or prenatal supplements that include adosage amount of DHA to meet the 300 mg/day recommendation is currentlyneeded to provide the DHA necessary for physiological benefits. Thus,one embodiment of the present invention includes compositions of thekits and methods of the present invention designed to optimize healthand wellness, minimize oxidative stress, and provide a beneficialincreased supplementation of DHA to meet the 300 mg/day recommendation.In one embodiment of the present invention the omega-3 fatty acid suchas DHA is provided in a separate dosage form from any other compositionof the kits and methods of the present invention. Moreover, such asupplementation for, e.g., a pregnant woman or nursing mother, is aviable means of providing physiologically active DHA not only to themother but also the infant.

DHA may be obtained in solid form, such as in a whole-cell microbialproduct, or in liquid form, such as in an oil. An example of DHA in oilform is DHASCO®-T vegetable oil from micro-algae (Martek BiosciencesCorporation, Columbia, Md.). Modes of producing DHA, or food products oradditives containing high concentrations of DHA, are known in the art.Some of these are described in U.S. Pat. Nos. 6,977,167; 5,407,957;5,492,938; 5,340,594; 6,410,281; 6,451,567; 5,340,594; 6,607,900;6,410,281; 6,451,567; and in U.S. Patent Application Publication Nos.2003/0060509 A1; 2006/0099693 A1; 2005/0170479 A1; and 2006/0165735 A1,the disclosure of all of which are expressly incorporated by referencein their entireties.

In one embodiment, the compositions of the methods and kits of thepresent invention may include omega-3 fatty acids in amounts rangingfrom about 125 mg to about 375 mg. In another embodiment, the methodsand kits of the present invention may include omega-3 fatty acids inamounts ranging from about 200 mg to about 300 mg. In yet anotherembodiment, the methods and kits of the present invention may includeomega-3 fatty acids in amounts ranging from about 225 mg to about 275mg. In a specific embodiment, the methods and kits of the presentinvention may include omega-3 fatty acids in an amount of about 250 mg.

In one embodiment, the methods and kits of the present invention mayinclude DHA in amounts ranging from about 125 mg to about 375 mg. Inanother embodiment, the methods and kits of the present invention mayinclude DHA in amounts ranging from about 200 mg to about 300 mg. In yetanother embodiment, the methods and kits of the present invention mayinclude DHA in amounts ranging from about 225 mg to about 275 mg. In aspecific embodiment, the methods and kits of the present invention mayinclude DHA in an amount of about 250 mg.

In another embodiment, the methods and kits of the present invention mayinclude DHA derived from algae. DHA derived from algae, as opposed tobeing derived from fish oil, has numerous beneficial effects. First, theDHA from algae does not have the “fishy” smell that can come with DHAfrom fish oil. Indeed, high doses of DHA from fish oil may result in thepatient having an unappealing after taste or a slight “fishy” body odoror “fishy” odor on the patient's breath. Second, DHA derived from algaecan be more easily regulated to assure consistency and further removethe risk of added chemicals or other dangers. For example, DHA fromalgae would not have the risk of being tainted with mercury as opposedto DHA from fish oil. Thus, DHA from algae provides pregnant women andneonate with DHA without this risk and dangers of mercury.

Each of the active ingredient vitamins, minerals and fatty acids of thepresent invention is available from numerous commercial sources, and inseveral active forms or salts thereof, as known to those of ordinaryskill in the art. Hence, the methods and kits of the present inventionare not limited to comprising or using any particular form of thevitamin, mineral or fatty acid ingredient described herein. Each of thevitamins, minerals and fatty acids can be blended to form a singlecomposition or can form multiple compositions, which may beco-administered.

The kits and methods of the present invention may comprise or use acombination of the included vitamins, nutrients and minerals justdescribed, in either chelated or non-chelated form. For example, thekits and methods of the present invention may include vitamin A, betacarotene, vitamin B₁, vitamin B₂, vitamin B₃, vitamin B₆, vitamin B₉,vitamin B₁₂, vitamin C, vitamin D₃, vitamin E, iron, magnesium, zinc andomega-3 fatty acids.

In another embodiment, the kits and methods of the present invention maycomprise a first composition comprising vitamin A, beta carotene,vitamin B₁, vitamin B₂, vitamin B₃, vitamin B₆, vitamin B₉, vitamin B₁₂,vitamin C, vitamin D₃, vitamin E, iron, magnesium and zinc; and a secondcomposition comprising omega-3 fatty acids.

In another embodiment, the first and second composition may beadministered to a patient. In another embodiment, the first and secondcomposition may be co-administered at the same time. In anotherembodiment, the first and second composition may be co-administered,wherein one composition is administered before the other composition, ineither order. In another embodiment, the first and second compositionmay be administered to the patient orally.

In another embodiment, the kits and methods of the present invention maycomprise swallowable compositions comprising vitamin A, beta carotene,vitamin B₁, vitamin B₂, vitamin B₃, vitamin B₆, vitamin B₉, vitamin B₁₂,vitamin C, vitamin D₃, vitamin E, iron, magnesium and zinc; anotherembodiment of the present invention may comprise swallowablecompositions comprising omega-3 fatty acids such as DHA enclosed withina gel-cap. Another specific embodiment of the present invention maycomprise compositions comprising omega-3 fatty acids such as DHA inliquid or oil form, in a bottle.

In another embodiment, the kits and methods of the present invention maycomprise a first composition consisting essentially of vitamin A, betacarotene, vitamin B₁, vitamin B₂, vitamin B₃, vitamin B₆, vitamin B₉,vitamin B₁₂, vitamin C, vitamin D₃, vitamin E, iron, magnesium and zinc;and a second composition consisting essentially of omega-3 fatty acids.

In another embodiment, the kits and methods of the present invention maycomprise a first composition consisting of vitamin A, beta carotene,vitamin B₁, vitamin B₂, vitamin B₃, vitamin B₆, vitamin B₉, vitamin B₁₂,vitamin C, vitamin D₃, vitamin E, iron, magnesium and zinc; and a secondcomposition consisting of omega-3 fatty acids.

In another embodiment, the kits and methods of the present invention maycomprise a first composition including about 550 IU to about 1650 IU ofvitamin A; about 300 IU to about 900 IU beta carotene; about 200 IU toabout 600 IU of vitamin D₃; about 30 mg to about 90 mg of vitamin C;about 15 IU to about 45 IU of vitamin E; about 0.5 mg to about 1.5 mg ofvitamin B₉; about 1.0 mg to about 3.0 mg of vitamin B₁; about 1.0 mg toabout 3.0 mg of vitamin B₂; about 7.0 mg to about 23 mg of vitamin B₃;about 1.0 mg to about 4.0 mg of vitamin B₆; about 2.0 mcg to about 8.0mcg of vitamin B₁₂; about 14 mg to about 44 mg of iron; about 12 mg toabout 38 mg of magnesium; and about 7.0 mg to about 23 mg of zinc.

In another embodiment, the kits and methods of the present invention maycomprise a second composition including about 125 mg to about 375 mgomega-3 fatty acids such as DHA.

In another embodiment, the kits and methods of the present invention maycomprise a first composition including about 880 IU to about 1320 IU ofvitamin A; about 480 IU to about 720 IU beta carotene; about 320 IU toabout 480 IU of vitamin D₃; about 48 mg to about 72 mg of vitamin C;about 24 IU to about 36 IU of vitamin E; about 0.8 mg to about 1.2 mg ofvitamin B₉; about 1.3 mg to about 1.9 mg of vitamin B₁; about 1.5 mg toabout 2.2 mg of vitamin B₂; about 12 mg to about 18 mg of vitamin B₃;about 2 mg to about 3 mg of vitamin B₆; about 4.0 mcg to about 6.0 mcgof vitamin B₁₂; about 23 mg to about 35 mg of iron; about 20 mg to about30 mg of magnesium; and about 12 mg to about 18 mg of zinc. In anotherembodiment, the kits and methods of the present invention may comprise asecond composition including about 187.5 mg to about 312.5 mg omega-3fatty acids such as DHA.

In another embodiment, the kits and methods of the present invention maycomprise a first composition including about 990 IU to about 1210 IU ofvitamin A; about 540 IU to about 660 IU beta carotene; about 360 IU toabout 440 IU of vitamin D₃; about 54 mg to about 66 mg of vitamin C;about 27 IU to about 33 IU of vitamin E; about 0.9 mg to about 1.1 mg ofvitamin B₉; about 1.5 mg to about 1.75 mg of vitamin B₁; about 1.6 mg toabout 2.0 mg of vitamin B₂; about 13.5 mg to about 16.5 mg of vitaminB₃; about 2.3 mg to about 2.8 mg of vitamin B₆; about 4.5 mcg to about5.5 mcg of vitamin B₁₂; about 26 mg to about 32 mg of iron; about 22.5mg to about 27.5 mg of magnesium; and about 13.5 mg to about 16.5 mg ofzinc. In another embodiment, the kits and methods of the presentinvention may comprise a second composition including about 225 mg toabout 275 mg omega-3 fatty acids such as DHA.

In another embodiment, the kits and methods of the present invention maycomprise a first composition including about 1100 IU of vitamin A; about600 IU beta carotene; about 400 IU of vitamin D₃; about 60 mg of vitaminC; about 30 IU of vitamin E; about 1.0 mg of vitamin B₉; about 1.6 mg ofvitamin B₁; about 1.8 mg of vitamin B₂; about 15 mg of vitamin B₃; about2.5 mg of vitamin B₆; about 5.0 mcg of vitamin B₁₂; about 29 mg of iron;about 25 mg of magnesium; and about 15 mg of zinc. In anotherembodiment, the kits and methods of the present invention may comprise asecond composition including about 250 mg omega-3 fatty acids such asDHA.

In another specific embodiment, the kits and methods of the presentinvention may include specific forms of each ingredient. For example,the kits and methods of the present invention may include vitamin A inthe form of acetate, beta carotene, vitamin B₁ in the form of thiaminemononitrate, vitamin B₂ in the form of riboflavin, vitamin B₃ in theform of niacinamide, vitamin B₆ in the form of pyridoxine hydrochloride,vitamin B₉ in the form of folic acid, vitamin B₁₂ in the form ofcyanocobalamin, vitamin C in the form of ascorbic acid, vitamin D₃ inthe form of cholecalciferol, vitamin E in the form of d-alpha-tocopherylacetate, iron in the form of polysaccharide iron complex, magnesium inthe form of magnesium oxide, zinc in the form of zinc oxide and omega-3fatty acids in the form of DHA.

In another embodiment, the kits and methods of the present invention maycomprise a first composition comprising vitamin A in the form ofacetate, beta carotene, vitamin B₁ in the form of thiamine mononitrate,vitamin B₂ in the form of riboflavin, vitamin B₃ in the form ofniacinamide, vitamin B₆ in the form of pyridoxine hydrochloride, vitaminB₉ in the form of folic acid, vitamin B₁₂ in the form of cyanocobalamin,vitamin C in the form of ascorbic acid, vitamin D₃ in the form ofcholecalciferol, vitamin E, in the form of d-alpha-tocopheryl acetate,iron in the form of polysaccharide iron complex, magnesium in the formof magnesium oxide and zinc in the form of zinc oxide; and a secondcomposition comprising omega-3 fatty acids in the form of DHA.

In another embodiment, the kits and methods of the present invention maycomprise swallowable compositions comprising vitamin A in the form ofacetate, beta carotene, vitamin B₁ in the form of thiamine mononitrate,vitamin B₂ in the form of riboflavin, vitamin B₃ in the form ofniacinamide, vitamin B₆ in the form of pyridoxine hydrochloride, vitaminB₉ in the form of folic acid, vitamin B₁₂ in the form of cyanocobalamin,vitamin C in the form of ascorbic acid, vitamin D₃ in the form ofcholecalciferol, vitamin E, in the form of d-alpha-tocopheryl acetate,iron in the form of polysaccharide iron complex, magnesium in the formof magnesium oxide and zinc in the form of zinc oxide; anotherembodiment of the present invention may comprise swallowablecompositions comprising omega-3 fatty acids in the form of DHA enclosedwithin a gel-cap. Another specific embodiment of the present inventionmay comprise compositions comprising omega-3 fatty acids in the form ofDHA in liquid or oil form, in a bottle.

In another specific embodiment, the swallowable compositions of thepresent invention may be in the form of gel-caps. Gel-caps consist of afiller comprising one or more pharmaceutically active materialsdissolved or dispersed in an appropriate liquid vehicle encapsulated ina gelatin shell generally comprising gelatin together with a plasticizersuch as glycerin or sorbitol. The filler material may comprise, forexample, polyethylene glycols. Gel-caps are well known to those ofordinary skill in the art. See for example, U.S. Pat. Nos. 4,780,316;5,419,916; 5,641,512; and 6,589,536. If more than one caplet or gel-capis used, each individual caplet or gel-cap may be identical to the othercaplets or gel-caps, or each may contain only some of the ingredients ofthe composition, so that the combination of the different caplets orgel-caps comprises a composition of the present invention. Anotherexemplary dosage of the compositions of the present invention mayconsist of one or more lozenges, the composition of each lozengepreferably being identical to each other lozenge. In another specificembodiment, the gel-cap may comprise sweeteners. In another specificembodiment, the gel-cap may comprise flavorants. In another specificembodiment, the flavorant may be orange flavor. In another specificembodiment, the gel-cap may comprise fillers. In another specificembodiment, the gel-cap may include active and/or inactive ingredientsin a liquid or oil form.

In another embodiment, the kits and methods of the present invention maycomprise a first composition consisting essentially of vitamin A in theform of acetate, beta carotene, vitamin B₁ in the form of thiaminemononitrate, vitamin B₂ in the form of riboflavin, vitamin B₃ in theform of niacinamide, vitamin B₆ in the form of pyridoxine hydrochloride,vitamin B₉ in the form of folic acid, vitamin B₁₂ in the form ofcyanocobalamin, vitamin C in the form of ascorbic acid, vitamin D₃ inthe form of cholecalciferol, vitamin E, in the form ofd-alpha-tocopheryl acetate, iron in the form of polysaccharide ironcomplex, magnesium in the form of magnesium oxide, and zinc in the formof zinc oxide; and a second composition consisting essentially ofomega-3 fatty acids in the form of DHA.

In another embodiment, the kits and methods of the present invention maycomprise a first composition consisting of vitamin A in the form ofacetate, beta carotene, vitamin B₁ in the form of thiamine mononitrate,vitamin B₂ in the form of riboflavin, vitamin B₃ in the form ofniacinamide, vitamin B₆ in the form of pyridoxine hydrochloride, vitaminB₉ in the form of folic acid, vitamin B₁₂ in the form of cyanocobalamin,vitamin C in the form of ascorbic acid, vitamin D₃ in the form ofcholecalciferol, vitamin E, in the form of d-alpha-tocopheryl acetate,iron in the form of polysaccharide iron complex, magnesium in the formof magnesium oxide, and zinc in the form of zinc oxide; and a secondcomposition consisting of omega-3 fatty acids in the form of DHA.

In another embodiment, the kits and methods of the present invention maycomprise a first composition including about 550 IU to about 1650 IU ofacetate; about 300 IU to about 900 IU beta carotene; about 200 IU toabout 600 IU of cholecalciferol; about 30 mg to about 90 mg of ascorbicacid; about 15 IU to about 45 IU of d-alpha-tocopheryl acetate; about0.5 mg to about 1.5 mg of folic acid; about 1.0 mg to about 3.0 mg ofthiamine mononitrate; about 1.0 mg to about 3.0 mg of riboflavin; about7.0 mg to about 23 mg of niacinamide; about 1.0 mg to about 4.0 mg ofpyridoxine hydrochloride; about 2.0 mcg to about 8.0 mcg ofcyanocobalamin; about 14 mg to about 44 mg of polysaccharide ironcomplex; about 12 mg to about 38 mg of magnesium oxide; and about 7.0 mgto about 23 mg of zinc oxide.

In another embodiment, the kits and methods of the present invention maycomprise a second composition including about 125 mg to about 375 mg ofDHA.

In another embodiment, the kits and methods of the present invention maycomprise a first composition including about 880 IU to about 1320 IU ofacetate; about 480 IU to about 720 IU beta carotene; about 320 IU toabout 480 IU of cholecalciferol; about 48 mg to about 72 mg of ascorbicacid; about 24 IU to about 36 IU of d-alpha-tocopheryl acetate; about0.8 mg to about 1.2 mg of folic acid; about 1.3 mg to about 1.9 mg ofthiamine mononitrate; about 1.5 mg to about 2.2 mg of riboflavin; about12 mg to about 18 mg of niacinamide; about 2 mg to about 3 mg ofpyridoxine hydrochloride; about 4.0 mcg to about 6.0 mcg ofcyanocobalamin; about 23 mg to about 35 mg of polysaccharide ironcomplex; about 20 mg to about 30 mg of magnesium oxide; and about 12 mgto about 18 mg of zinc oxide. In another embodiment, the kits andmethods of the present invention may comprise a second compositionincluding about 200 mg to about 300 mg of DHA.

In another embodiment, the kits and methods of the present invention maycomprise a first composition including about 990 IU to about 1210 IU ofacetate; about 540 IU to about 660 IU beta carotene; about 360 IU toabout 440 IU of cholecalciferol; about 54 mg to about 66 mg of ascorbicacid; about 27 IU to about 33 IU of d-alpha-tocopheryl acetate; about0.9 mg to about 1.1 mg of folic acid; about 1.5 mg to about 1.75 mg ofthiamine mononitrate; about 1.6 mg to about 2.0 mg of riboflavin; about13.5 mg to about 16.5 mg of niacinamide; about 2.3 mg to about 2.8 mg ofpyridoxine hydrochloride; about 4.5 mcg to about 5.5 mcg ofcyanocobalamin; about 26 mg to about 32 mg of polysaccharide ironcomplex; about 22.5 mg to about 27.5 mg of magnesium oxide; and about13.5 mg to about 16.5 mg of zinc oxide. In another embodiment, the kitsand methods of the present invention may comprise a second compositionincluding about 225 mg to about 275 mg of DHA.

In another embodiment, the kits and methods of the present invention maycomprise a first composition including about 1100 IU of acetate; about600 IU beta carotene; about 400 IU of cholecalciferol; about 60 mg ofascorbic acid; about 30 IU of d-alpha-tocopheryl acetate; about 1.0 mgof folic acid; about 1.6 mg of thiamine mononitrate; about 1.8 mg ofriboflavin; about 15 mg of niacinamide; about 2.5 mg of pyridoxinehydrochloride; about 5.0 mcg of cyanocobalamin; about 29 mg ofpolysaccharide iron complex; about 25 mg of magnesium oxide; and about15 mg of zinc oxide. In another embodiment, the kits and methods of thepresent invention may comprise a second composition including about 250mg of DHA.

The active ingredients are available from numerous commercial sources,and in several active forms or salts thereof, known to those of ordinaryskill in the art. Hence, the kits and methods of the present inventionare not limited to comprising or using any particular form of thevitamin or mineral ingredient described herein.

B-complex vitamins, such as vitamin B₆ and B₁₂, vitamin D₃, andmagnesium play integral roles in physiological mechanisms that serve toprevent, treat and/or alleviate the occurrence or negative effects ofcardiovascular disease, colorectal cancer and osteoporosis.Supplementation with vitamins and minerals such as vitamin K may inhibitthese beneficial effects. Thus, when creating or choosing a nutritionalsupplement, it is essential to understand the physiological needs andrisks of individual patients and population groups and the interactionsbetween various vitamins and minerals.

For example, vitamin K may have deleterious effects. Although vitamin K,or phylloquinone, plays a role in the process of maintaining bonehealth, it also plays a major role in the synthesis of coagulationfactors. This delicate balance of coagulation is at times purposefullyaltered in those with, or at high risk of, cardiovascular disease.Increased intake of vitamin K can alter the efficacy of specificmedications used for this purpose. Further, the human body producesvitamin K from naturally occurring intestinal bacteria, thus makingdeficiency of this nutrient rare. Due to these factors, broad spectrumvitamin K supplementation is discouraged. Kurnik et al., 37(11) ANN.PHARMACOTHER. 1603-06 (2003); Shearer, 345 LANCET 229-34 (1995). In aspecific embodiment, the compositions of the kits and methods of thepresent invention may be substantially free of added vitamin K.

In another example, lactose is a disaccharide, or sugar that is foundmainly in milk and dairy products. Lactose intolerance or the inabilityto properly digest and absorb this compound is relatively common. Withthis inability comes uncomfortable side effects such as abdominalbloating, pain, and diarrhea upon ingestion of lactose-containing foods.Since milk and dairy products are a primary source of both calcium andlactose, those who are lactose intolerant are more likely to haveinsufficient calcium intake and therefore osteoporosis. DiStefano etal., 122(7) GASTROENTEROL. 1793-99 (2002). In a specific embodiment, thecompositions of the kits and methods of the present invention may befree of added lactose.

In another example, copper may be added in prenatal nutritionalsupplements to serve a role in protecting against disease andcontributes to the overall health of the mother and developing child.Copper, however, may have adverse side effects outweighing any potentialbenefits. For example, high elevated serum levels of copper have beenassociated with post-partum depression. J W Crayton et al., J TRACE ELEMMED BIOL 21(1): 17-21 (2007). Thus, it is suggested that women who arepregnant or plan to become pregnant with a history of post-partumdepression should carefully consider supplementation with copper. Id.Further, for this reason, copper may have deleterious effects onvitamins, antioxidants, nutrients or minerals of the present inventionthat are associated with reducing post-partum depression, such as DHA.In a specific embodiment, the compositions of the kits and methods ofthe present invention may be substantially free of added copper.

In another example, calcium may be added in prenatal nutritionalsupplements to serve a role in proper functioning of numerousintracellular and extracellular processes including, for example, musclecontraction, nerve conduction, blood coagulation, and of particularinterest in the context of pregnancy and lactation and hormone release.Calcium, however, when added in high doses in nutritional supplements,can have undesirable side effects such as, constipation and otherstomach problems such as nausea, vomiting and cramps. In a specificembodiment, the compositions of the kits and methods of the presentinvention may be substantially free of added calcium.

Manganese is a trace element essential for adequate growth andreproduction, bone development and carbohydrate metabolism. PRESENTKNOWLEDGE IN NUTRITION 7th Ed., pp. 334-339, E E Ziegler and L J Filer,Jr. eds., ILSI Press, Washington, D.C. (1996). As such, it is commonlyincluded in nutritional supplements. Manganese toxicity, however, isalso recognized as a serious health hazard to humans, when the mineralis taken in excess doses. Id. This toxicity may result in severeabnormalities of the central nervous system. Id. Manganese toxicity hasbeen reported in an individual who consumed high amounts of manganesesupplements over an extended period of time, and individuals whoconsumed water containing high manganese concentrations. Id. In aspecific embodiment, the compositions of the methods and kits of thepresent invention may be substantially free of added manganese.

Thus, the kits and methods of the present invention provide a vitamin,mineral, and omega-3 fatty acid (such as DHA) supplementation thatexcludes ingredients that have deleterious effects on omega-3 fattyacids (such as DHA) or other undesirable side effects. Further, the kitsand methods of the present invention provide a conservative ornon-excessive amount of various ingredients to reduce the risk ofundesirable side effects but still provide adequate nutritionalsupplementation for each ingredient. The kits and methods of the presentinvention may therefore be desirable for nutritional supplementationduring periods such as prior to conception, throughout pregnancy, andduring the postnatal period for lactating and non-lactating mother.

Specific patients, however, may also have unique or rare adversereactions to antioxidants, vitamins or minerals added in thecompositions of the present invention. Indeed, when choosing andadministering a nutritional supplement, it is essential to understandthe physiological needs and risks of individual patients and particularpopulation groups, and the interactions between various vitamins andminerals. Thus, in particular instances, the compositions and methods ofthe present invention may also be substantially free of one or more ofthe added specific antioxidants, vitamins, nutrients or minerals in thecompounds of the present invention to address such needs and risks.

In one specific embodiment, the kits and methods of the presentinvention may be substantially free of added vitamin A. In oneembodiment, the compositions of the kits and methods of the presentinvention may be substantially free of added beta carotene. In oneembodiment, the compositions of the kits and methods of the presentinvention may be substantially free of added vitamin D₃. In oneembodiment, the compositions of the kits and methods of the presentinvention may be substantially free of added vitamin E. In oneembodiment, the compositions of the kits and methods of the presentinvention may be substantially free of added vitamin B₉. In oneembodiment, the compositions of the kits and methods of the presentinvention may be substantially free of added vitamin B₁. In oneembodiment, the compositions of the kits and methods of the presentinvention may be substantially free of added vitamin B₂. In oneembodiment, the compositions of the kits and methods of the presentinvention may be substantially free of added vitamin B₆. In oneembodiment, the compositions of the kits and methods of the presentinvention may be substantially free of added vitamin B₁₂. In oneembodiment, the compositions of the kits and methods of the presentinvention may be substantially free of added vitamin B₃.

In a specific embodiment of the present invention, other specificvitamins, nutrients and/or minerals may be excluded. For example, in aspecific embodiment, the compositions of the kits and methods of thepresent invention may be substantially free of added alpha carotene;substantially free of added lutein; substantially free of addedlycopene; substantially free of added zeaxanthin; substantially free ofadded vitamin B₄; substantially free of added vitamin B₅; substantiallyfree of added vitamin B₇; substantially free of added vitamin B₈;substantially free of added vitamin B₁₀; substantially free of addedvitamin B₁₁; substantially free of added calcium; substantially free ofadded chromium; substantially free of added copper; substantially freeof added manganese; substantially free of added selenium; substantiallyfree of added boron; substantially free of added odorless garlic;substantially free of added coenzyme Q-10; substantially free of addedl-carnitine; substantially free of added grape seed extract;substantially free of added green tea extract; substantially free ofadded quercetin; substantially free of added hawthorne berries; and/orsubstantially free of added alpha lipoic acid. In another embodiment ofthe present invention, the compositions are substantially free of otheradded vitamins and minerals.

In another specific embodiment, the compositions of the kits and methodsof the present invention may be substantially free of one or more ofadded active compounds selected from the group consisting of lutein,lycopene, zeaxanthin, vitamin B₄, vitamin B₅, vitamin B₇, vitamin B₈,vitamin B₁₀, vitamin K, biotin, pantothenic acid, phosphorus, iodine,potassium, odorless garlic, coenzyme Q₁₀, l-carnitine, grape seedextract, chloride, sodium, green tea extract, quercetin, fluoride,hawthorne berries, and alpha lipoic acid.

In another specific embodiment, the compositions of the kits and methodsof the present invention may be substantially free of one or more ofadded minerals and compounds selected from the group consisting of,copper, calcium, chromium, titanium, molybdenum, nickel, tin, silicon,vanadium, manganese, selenium, selenite, boron, bismuth, borax, bauxite,gold, silver, hydroxylapatite, mica, quartz, steatite, talc, sulfur, andzircon.

In another specific embodiment, the compositions of the kits and methodsof the present invention may be substantially free of one or more ofadded inactive compounds selected from the group consisting of magnesiumstearate, silica, silicon dioxide, magnesium silicate, dicalciumphosphate, povidone, titanium dioxide, sodium benzoate, alpha lipoicacid, lutein, lycopene, cellulose, croscarmellose sodium, stearic acid,cellulose, hydroxylpropyl cellulose, hydroxypropyl methylcellulose,titanium dioxide, polydextrose, triacetin, dicalcium phosphate,polyethylene glycol, polyvinylpyrrolidone, mineral oil, methocel, sodiumlauryl sulfate, and talc.

A specific embodiment of the present invention may comprise swallowablecompositions. Swallowable compositions are well known in the art and arethose that do not readily dissolve when placed in the mouth and may beswallowed whole without any chewing or discomfort. In a specificembodiment of the present invention the swallowable compositions mayhave a shape containing no sharp edges and a smooth, uniform andsubstantially bubble free outer coating.

To prepare the swallowable compositions of the present invention, eachof the active ingredients may be combined in intimate admixture with asuitable carrier according to conventional compounding techniques. In aspecific embodiment of the swallowable compositions of the presentinvention, the surface of the compositions may be coated with apolymeric film. Such a film coating has several beneficial effects.First, it reduces the adhesion of the compositions to the inner surfaceof the mouth, thereby increasing the patient's ability to swallow thecompositions. Second, the film may aid in masking the unpleasant tasteof certain drugs. Third, the film coating may protect the compositionsof the present invention from atmospheric degradation. Polymeric filmsthat may be used in preparing the swallowable compositions of thepresent invention include vinyl polymers such as polyvinylpyrrolidone,polyvinyl alcohol and acetate, cellulosics such as methyl and ethylcellulose, hydroxyethyl cellulose and hydroxylpropyl methylcellulose,acrylates and methacrylates, copolymers such as the vinyl-maleic acidand styrene-maleic acid types, and natural gums and resins such as zein,gelatin, shellac and acacia. Pharmaceutical carriers and formulationsfor swallowable compounds are well known to those of ordinary skill inthe art. See generally, e.g., WADE & WALLER, HANDBOOK OF PHARMACEUTICALEXCIPIENTS (2^(nd) ed. 1994).

In a specific embodiment of the present invention, the compositions maycomprise chewable compositions. Chewable compositions are those thathave a palatable taste and mouthfeel, are relatively soft and quicklybreak into smaller pieces and begin to dissolve after chewing such thatthey are swallowed substantially as a solution.

In order to create chewable compositions, certain ingredients should beincluded to achieve the attributes just described. For example, chewablecompositions should include ingredients that create pleasant flavor andmouthfeel and promote relative softness and dissolvability in the mouth.The following discussion describes ingredients that may help to achievethese characteristics.

Chewable compositions preferably have a pleasant or palatable flavor.Palatable flavors may be achieved by including sweetening agents and/orflavorants. Sweetening agents that may be included in the compositionsof the present invention include, by way of example and withoutlimitation, sucrose, fructose, high fructose corn syrup, dextrose,saccharin sodium, maltodextrin, aspartame, potassium acesulfame,neohesperidin dihydrochalcone, sucralose, monoammonium glycyrrhizinate,and others known to those of ordinary skill in the art. As used herein,the term “flavorant” means natural or artificial compounds used toimpart a pleasant flavor and often odor to a pharmaceutical preparation.Flavorants that may be used in the present invention include, forexample and without limitation, natural and synthetic flavor oils,flavoring aromatics, extracts from plants, leaves, flowers, and fruitsand combinations thereof. Such flavorants include, by way of example andwithout limitation, anise oil, cinnamon oil, vanilla, vanillin, cocoa,chocolate, natural chocolate flavor, menthol, grape, peppermint oil, oilof wintergreen, clove oil, bay oil, anise oil, eucalyptus, thyme oil,cedar leave oil, oil of nutmeg, oil of sage, oil of bitter almonds,cassia oil; citrus oils, such as lemon, orange, lime and grapefruitoils; and fruit essences, including apple, pear, peach, berry,wildberry, date, blueberry, kiwi, strawberry, raspberry, cherry, plum,pineapple, and apricot. All of these flavorants are commerciallyavailable. In a specific embodiment of the present invention, flavorantsthat may be used include natural berry extracts and natural mixed berryflavor, as well as citric and malic acid. The amount of flavorants usedmay depend on a number of factors, including desired tastecharacteristics. While not necessary, one or more of these sweeteningagents and/or flavorants also may be included in the swallowablecompositions of the present invention. In a specific embodiment, thechewable compositions may have a natural berry flavor.

In addition to having a palatable flavor, chewable compositions alsoshould have a pleasant mouthfeel. A variety of ingredients can beincluded in the compositions of the present invention to enhancemouthfeel.

In the chewable compositions of the present invention, sugars such aswhite sugar, corn syrup, sorbitol (solution), maltitol (syrup),oligosaccharide, isomaltooligosaccharide, sucrose, fructose, lactose,glucose, lycasin, xylitol, lactitol, erythritol, mannitol, isomaltose,dextrose, polydextrose, dextrin, compressible cellulose, compressiblehoney, compressible molasses and mixtures thereof may be added toimprove mouthfeel and palatability. Further, by way of example andwithout limitation, fondant or gums such as gelatin, agar, arabic gum,guar gum, and carrageenan may be added to improve the chewiness of thecompositions. Fatty materials that may be included in the presentinvention include, by way of example and without limitation, vegetableoils (including palm oil, palm hydrogenated oil, corn germ hydrogenatedoil, castor hydrogenated oil, cotton-seed oil, olive oil, peanut oil,palm olein oil, and palm stearin oil), animal oils (including refinedoil and refined lard whose melting point ranges from 30° to 42° C.),Cacao fat, margarine, butter, and shortening.

Alkyl polysiloxanes (commercially available polymers sold in a varietyof molecular weight ranges and with a variety of different substitutionpatterns) also may be used in the present invention to enhance thetexture, the mouthfeel, or both of the chewable nutritional supplementcompositions described herein. By “enhance the texture” it is meant thatthe alkyl polysiloxane improves one or more of the stiffness, thebrittleness, and the chewiness of the chewable supplement, relative tothe same preparation lacking the alkyl polysiloxane. By “enhance themouthfeel” it is meant that the alkyl polysiloxane reduces the grittytexture of the supplement once it has liquefied in the mouth, relativeto the same preparation lacking the alkyl polysiloxane.

Alkyl polysiloxanes generally comprise a silicon and oxygen-containingpolymeric backbone with one or more alkyl groups pending from thesilicon atoms of the back bone. Depending upon their grade, they canfurther comprise silica gel. Alkyl polysiloxanes are generally viscousoils. Exemplary alkyl polysiloxanes that can be used in the swallowable,chewable or dissolvable compositions of the present invention include,by way of example and without limitation, monoalkyl or dialkylpolysiloxanes, wherein the alkyl group is independently selected at eachoccurrence from a C₁-C₆-alkyl group optionally substituted with a phenylgroup. A specific alkyl polysiloxane that may be used is dimethylpolysiloxane (generally referred to as simethicone). More specifically,a granular simethicone preparation designated simethicone GS may beused. Simethicone GS is a preparation which contains 30% simethiconeUSP. Simethicone USP contains not less than about 90.5% by weight(CH₃)₃—Si{OSi(CH₃)₂}CH₃ in admixture with about 4.0% to about 7.0% byweight SiO₂.

To prevent the stickiness that can appear in conventional chewablecompositions and to facilitate conversion of the active ingredients toemulsion or suspension upon taking, the compositions of the presentinvention, may further comprise emulsifiers such as, by way of exampleand without limitation, glycerin fatty acid ester, sorbitanmonostearate, sucrose fatty acid ester, lecithin and mixtures thereof.In a specific embodiment, one or more of such emulsifiers may be presentin an amount of about 0.01% to about 5.0%, by weight of the administeredcompositions. If the level of emulsifier is lower or higher than thesaid range, the emulsification cannot be realized, or wax value willrise.

Chewable compositions should begin to break and dissolve in the mouthshortly after chewing begins such that the compositions can be swallowedsubstantially as a solution. The dissolution profile of chewablecompositions may be enhanced by including rapidly water-soluble fillersand excipients. Rapidly water-soluble fillers and excipients preferablydissolve within about 60 seconds of being wetted with saliva. Indeed, itis contemplated that if enough water-soluble excipients are included inthe compositions of the present invention, they may become dissolvablerather than chewable composition forms. Examples of rapidly watersoluble fillers suitable for use with the present invention include, byway of example and without limitation, saccharides, amino acids and thelike. In a specific embodiment, the saccharide may be a mono-, di- oroligosaccharide. Examples of saccharides which may be added to thecompositions of the present invention include, by way of example andwithout limitation, sorbitol, glucose, dextrose, fructose, maltose andxylitol (all monosaccharides); and sucrose, lactose, glucose, galactoseand mannitol (all disaccharides). Other suitable saccharides areoligosaccharides. Examples of oligosaccharides are dextrates andmaltodextrins. Other water soluble excipients that may be used with thepresent invention include, by way of example and without limitation,amino acids such as alanine, arginine, aspartic acid, asparagine,cysteine, glutamic acid, glutamine, glycine, histidine, isoleucine,leucine, lysine, methionine, phenylalanine, proline, serine, threonine,tryptophan, tyrosine and valine.

Disintegrants also may be included in the compositions of the presentinvention in order to facilitate dissolution. Disentegrants, includingpermeabilising and wicking agents, are capable of drawing water orsaliva up into the compositions which promotes dissolution from theinside as well as the outside of the compositions. Such disintegrants,permeabilising and/or wicking agents that may be used in the presentinvention include, by way of example and without limitation, starches,such as corn starch, potato starch, pre-gelatinized and modifiedstarches thereof, cellulosic agents, such as Ac-di-sol, montmorriloniteclays, cross-linked PVP, sweeteners, bentonite, microcrystallinecellulose, croscarmellose sodium, alginates, sodium starch glycolate,gums, such as agar, guar, locust bean, karaya, pectin, Arabic, xanthanand tragacanth, silica with a high affinity for aqueous solvents, suchas colloidal silica, precipitated silica, maltodextrins,beta-cyclodextrins, polymers, such as carbopol, and cellulosic agents,such as hydroxymethylcellulose, hydroxypropylcellulose andhydroxyopropylmethylcellulose.

Finally, dissolution of the compositions may be facilitated by includingrelatively small particles sizes of the ingredients used.

In addition to those described above, any appropriate fillers andexcipients may be utilized in preparing the swallowable, chewable and/ordissolvable compositions of the present invention so long as they areconsistent with the objectives described herein. For example, bindersare substances used to cause adhesion of powder particles ingranulations. Such compounds appropriate for use in the presentinvention include, by way of example and without limitation, acacia,compressible sugar, gelatin, sucrose and its derivatives, maltodextrin,cellulosic polymers, such as ethylcellulose, hydroxypropylcellulose,hydroxypropylmethyl cellulose, carboxymethylcellulose sodium andmethylcellulose, acrylic polymers, such as insoluble acrylateammoniomethacrylate copolymer, polyacrylate or polymethacryliccopolymer, povidones, copovidones, polyvinylalcohols, alginic acid,sodium alginate, starch, pregelatinized starch, guar gum, polyethyleneglycol and others known to those of ordinary skill in the art.

Diluents also may be included in the compositions of the presentinvention in order to enhance the granulation of the compositions.Diluents can include, by way of example and without limitation,microcrystalline cellulose, sucrose, dicalcium phosphate, starches,lactose and polyols of less than 13 carbon atoms, such as mannitol,xylitol, sorbitol, maltitol and pharmaceutically acceptable amino acids,such as glycin, and their mixtures.

Lubricants are substances used in composition formulations that reducefriction during composition compression. Lubricants that may be used inthe present invention include, by way of example and without limitation,stearic acid, calcium stearate, magnesium stearate, zinc stearate, talc,mineral and vegetable oils, benzoic acid, poly(ethylene glycol),glyceryl behenate, stearyl fumarate, and others known to those ofordinary skill in the art.

Glidants improve the flow of powder blends during manufacturing andminimize composition weight variation. Glidants that may be used in thepresent invention include, by way of example and without limitation,silicon dioxide, colloidal or fumed silica, magnesium stearate, calciumstearate, stearic acid, cornstarch, talc and others known to those ofordinary skill in the art.

Colorants also may be included in the nutritional supplementcompositions of the present invention. As used herein, the term“colorant” includes compounds used to impart color to pharmaceuticalpreparations. Such compounds include, by way of example and withoutlimitation, FD&C Red No. 3, FD&C Red No. 20, FD&C Yellow No. 6, FD&CBlue No. 2, D&C Green No. 5, FD&C Orange No. 5, D&C Red No. 8, caramel,and ferric oxide, red and others known to those of ordinary skill in theart. Coloring agents also can include pigments, dyes, tints, titaniumdioxide, natural coloring agents, such as grape skin extract, beet redpowder, beta carotene, annato, carmine, turmeric, paprika and othersknown to those of ordinary skill in the art. It is recognized that nocolorant is required in the nutritional supplement compositionsdescribed herein.

If desired, the compositions of the present invention may be sugarcoated or enteric coated by standard techniques. The unit dose forms maybe individually wrapped, packaged as multiple units on paper strips orin vials of any size, without limitation. The swallowable, chewable ordissolvable compositions of the present invention may be packaged inunit dose, rolls, bulk bottles, blister packs and combinations thereof,without limitation.

The swallowable, chewable or dissolvable compositions of the presentinvention may be prepared using conventional methods and materials knownin the pharmaceutical art. For example, U.S. Pat. Nos. 5,215,754 and4,374,082 relate to methods for preparing swallowable compositions. U.S.Pat. No. 6,495,177 relates to methods to prepare chewable nutritionalsupplements with improved mouthfeel. U.S. Pat. No. 5,965,162, relates tokits and methods for preparing multi-vitamin comestible units whichdisintegrate quickly in the mouth, especially when chewed. Further, allpharmaceutical carriers and formulations described herein are well knownto those of ordinary skill in the art, and determination of workableproportions in any particular instance will generally be within thecapability of the person skilled in the art. Details concerning any ofthe excipients of the invention may be found in WADE & WALLER, HANDBOOKOF PHARMACEUTICAL EXCIPIENTS (2nd ed. 1994). All active ingredients,fillers and excipients are commercially available from companies such asAldrich Chemical Co., FMC Corp, Bayer, BASF, Alexi Fres, Witco,Mallinckrodt, Rhodia, ISP, and others.

A specific embodiment of the present invention may comprise swallowablecompositions packaged in blister packs. Blister packs as packaging forswallowable compositions are well known to those of ordinary skill inthe art. Blister packs may be made of a transparent plastic sheet whichas been formed to carry a matrix of depression or blisters. One or moreswallowable compositions are received in each depression or blister. Afoil or plastic backing is then adhered across the plane of the sheetsealing the swallowable compositions in their respective blisters.Examples of materials used for the blister packs include, but are notlimited to, aluminum, paper, polyester, PVC, and polypropylene.Alternative materials are known to those of ordinary skill in the art.To remove a swallowable composition, the depression material is pressedin and the composition is pushed through the backing material. Multipleblister packs may be placed in an outer package, often a box or cartonfor sale and distribution.

Another specific embodiment of the present invention may compriseswallowable compositions packaged in bottles. The bottle may be glass orplastic in form with a pop or screw top cap. Bottle packaging forcompositions in swallowable form are well known to those of ordinaryskill in the art.

Additionally, the unit dose forms may be individually wrapped, packagedas multiple units on paper strips or in vials of any size, withoutlimitation. The swallowable, chewable or dissolvable compositions of theinvention may be packaged in unit dose, rolls, bulk bottles, blisterpacks and combinations thereof, without limitation.

Other objectives, features and advantages of the present invention willbecome apparent from the following specific examples. The specificexamples, while indicating specific embodiments of the invention, areprovided by way of illustration only. Accordingly, the present inventionalso includes those various changes and modifications within the spiritand scope of the invention that may become apparent to those skilled inthe art from this detailed description. The invention will be furtherillustrated by the following non-limiting examples.

EXAMPLES

Without further elaboration, it is believed that one skilled in the art,using the preceding description, can utilize the present invention tothe fullest extent. The following examples are illustrative only, andnot limiting of the remainder of the disclosure in any way whatsoever.

Example 1

A first composition of the following formulation is prepared in chewableform, including the appropriate excipients, by standard methods known tothose of ordinary skill in the art:

Vitamin A (acetate) 1100 IU Beta Carotene 600 IU Vitamin B₁ (thiaminemononitrate) 1.6 mg Vitamin B₂ (riboflavin) 1.8 mg Vitamin B₃(niacinamide) 15 mg Vitamin B₆ (pyridoxine hydrochloride) 2.5 mg VitaminB₉ (folic acid) 1000 μg Vitamin B₁₂ (cyanocobalamin) 5 μg Vitamin C(ascorbic acid) 60 mg Vitamin D (cholecalciferol) 400 IU Vitamin E(d-alpha-tocopheryl acetate) 30 IU Iron (polysaccharide complex) 29 mgMagnesium (magnesium oxide) 25 mg Zinc (zinc oxide) 15 mg

A second composition of the following formulation is prepared in gel-capform by standard methods known to those of ordinary skill in the art:

DHA, an omega-3 fatty acid 250 mg

Example 2

A study is undertaken to evaluate the effectiveness of the compositionsof the present invention in the treatment of patients. The objective ofthe study is to determine whether oral intake of the compositionsresults in an improvement of the nutritional status of patients withregard to the specific vitamins and minerals contained in theadministered compositions.

A double-blind, placebo controlled study is conducted over a six-monthperiod. A total of 120 subjects (60 pregnant women entering the secondtrimester of pregnancy and 60 lactating women), aged 20-35 years, arechosen for the study. An initial assessment of the nutritional status ofeach woman is conducted. Vitamin A, beta carotene and vitamin B₆ aremeasured using high performance liquid chromatography. Erythrocytetransketolase activity is used to measure vitamin B₁ levels. Vitamin B₂levels are determined by assessment of erythrocyte glutathione reductaseactivity. Vitamin B₃ levels are assessed by measuring urinary excretionof N′methylnicotinamide and its pyridone. Vitamin B₉ is measured byradioimmunoassay (RIA), specifically The Solid Phase No Biol Folic AcidKit (Diagnostic Products, Los Angeles, Calif.). Vitamin B₁₂ is measuredby RIA using human intrinsic factor as a binder. Vitamin C levels aremeasured by spectrophotometric and colorimetric methods. Vitamin D ismeasured using an extraction double-antibody RIA (Dia Sorin, Inc.,Stillwater, Minn.). The peroxide hemolysis test is used to determinevitamin E status. Iron levels are measured using standardspectrophotometry. Similarly, magnesium levels are measured byabsorbance of a magnesium chelate with xylidl blue at 660 nM. Zinclevels are assessed using flame atomic absorption spectrometry (PerkinsElmer 460, Norwalk, Conn.). DHA is measured and quantified using gaschromatography procedures.

Additionally, total serum homocysteine levels are determined byextraction on the Multi-Prep® gravity series GVSA-100 column, a stronganion exchange gravity flow column, and measurement by gaschromatography/mass spectrometry. Biochemical Diagnostics, Austin, Tex.

The 120 subjects are separated into four separate groups of 30 women. Ina first group comprising only pregnant women and in a second groupcomprising only lactating women, each subject is administered one dosageform of the composition as described in Example 1 twice a day. In athird group comprising only pregnant women and in a fourth groupcomprising only lactating women, each subject is administered oneplacebo dosage form twice a day. Thus, dosage form administration occursevery 12 hours. No other nutritional supplements are taken by thesubjects during the assessment period.

An assessment of the nutritional status of each woman is conductedutilizing the methods described above at one month intervals for a sixmonth period. The data is evaluated using multiple linear regressionanalysis and a standard t-test. In each analysis, the baseline value ofthe outcome variable is included in the model as a covariant. Treatmentby covariant interaction effects is tested by the method outlined byWeigel & Narvaez, 12 CONTROLLED CLINICAL TRIALS 378-94 (1991). If thereare no significant interaction effects, the interaction terms areremoved from the model. The regression model assumptions of normalityand homogeneity of variance of residuals are evaluated by inspection ofthe plots of residuals versus predicted values. Detection of thetemporal onset of effects is done sequentially by testing for thepresence of significant treatment effects at 1, 2, 3, 4, 5, and 6months, proceeding to the earlier time in sequence only when significanteffects have been identified at each later time period. Changes from thebaseline within each group are evaluated using paired t-tests. Inaddition, analysis of variance is performed on all baseline measurementsand measurable subject characteristics to assess homogeneity betweengroups. All statistical procedures are conducted using the StatisticalAnalysis System (SAS Institute Inc., Cary, N.C.). An alpha level of 0.05is used in all statistical tests.

A statistically significant improvement in the nutritional status ofvitamin, mineral, and DHA levels measured is observed in the treatedsubjects over the controls upon completion of the study. Homocysteinelevels in women receiving supplements remain unelevated. Therefore, thestudy confirms that oral administration of the compositions of thepresent invention is effective in improving the nutritional status ofpatients. The length of gestation is increased by approximately six daysin women receiving supplements, due to DHA intake, and theirhomocysteine levels are not elevated, due to folic acid intake, leadingto a better prognosis regarding risk of neural tube defects in theirinfants.

While specific embodiments of the present invention have been described,other and further modifications and changes may be made withoutdeparting from the spirit of the invention. All further and othermodifications and changes are included that come within the scope of theinvention as set forth in the claims. The disclosure of each publicationcited above is expressly incorporated by reference in its entirety tothe same extent as if each were incorporated by reference individually.

What is claimed is:
 1. A kit comprising: a first flavored and chewablecomposition comprising vitamins and minerals and one or morepharmaceutically-acceptable carriers, wherein the vitamins and mineralsbeing one or more selected from the group consisting of: vitamin A, betacarotene, vitamin B₁, vitamin B₂, vitamin B₃, vitamin B₆, vitamin B₉,vitamin B₁₂, vitamin C, vitamin D₃, vitamin E, iron, magnesium and zinc,and wherein the one or more pharmaceutically-acceptable carriers; and asecond flavored soft gel composition comprising omega-3 fatty acids andone or more pharmaceutically-acceptable carriers.
 2. The kit of claim 1,wherein the one or more pharmaceutically-acceptable carriers for thefirst composition comprises one or both of a flavorant and a sweetener.3. The kit of claim 2, wherein the flavorant is one or more selectedfrom the group consisting of: natural flavor oils, synthetic flavoroils, flavoring aromatics, extracts from plants, extracts from leaves,extracts from flowers, extracts from fruits, anise oil, cinnamon oil,vanilla, vanillin, cocoa, chocolate, natural chocolate flavor, menthol,grape, peppermint oil, oil of wintergreen, clove oil, bay oil, aniseoil, eucalyptus, thyme oil, cedar leave oil, oil of nutmeg, oil of sage,oil of bitter almonds, cassia oil, citrus oil, lemon oil, orange oil,lime oil, grapefruit oil, fruit essence, apple essence, pear essence,peach, berry essence, wildberry essence, date essence, blueberryessence, kiwi essence, strawberry essence, raspberry essence, cherryessence, plum essence, pineapple essence, and apricot essence.
 4. Thekit of claim 1, wherein the one or more pharmaceutically-acceptablecarriers for the second composition comprises one or both of a flavorantand a sweetener.
 5. The kit of claim 4, wherein the flavorant is one ormore selected from the group consisting of: natural flavor oils,synthetic flavor oils, flavoring aromatics, extracts from plants,extracts from leaves, extracts from flowers, extracts from fruits, aniseoil, cinnamon oil, vanilla, vanillin, cocoa, chocolate, naturalchocolate flavor, menthol, grape, peppermint oil, oil of wintergreen,clove oil, bay oil, anise oil, eucalyptus, thyme oil, cedar leave oil,oil of nutmeg, oil of sage, oil of bitter almonds, cassia oil, citrusoil, lemon oil, orange oil, lime oil, grapefruit oil, fruit essence,apple essence, pear essence, peach, berry essence, wildberry essence,date essence, blueberry essence, kiwi essence, strawberry essence,raspberry essence, cherry essence, plum essence, pineapple essence, andapricot essence.
 6. The kit of claim 2, wherein the one or morepharmaceutically-acceptable carriers for the first composition comprisesa sweetening agent.
 7. The kit of claim 6, wherein the sweetening agentis one or more selected from the group consisting of: sucrose, fructose,high fructose corn syrup, dextrose, saccharin sodium, maltodextrin,aspartame, potassium acesulfame, neohesperidin dihydrochalcone,sucralose, and monoammonium glycyrrhizinate.
 8. The kit of claim 2,wherein the one or more pharmaceutically-acceptable carriers for thesecond composition comprises a sweetening agent.
 9. The kit of claim 8,wherein the sweetening agent is one or more selected from the groupconsisting of: sucrose, fructose, high fructose corn syrup, dextrose,saccharin sodium, maltodextrin, aspartame, potassium acesulfame,neohesperidin dihydrochalcone, sucralose, and monoammoniumglycyrrhizinate.
 10. The kit of claim 1, wherein the first compositioncomprises vitamin A, beta carotene, vitamin B₁, vitamin B₂, vitamin B₃,vitamin B₆, vitamin B₉, vitamin B₁₂, vitamin C, vitamin D₃, vitamin E,iron, magnesium and zinc.
 11. The kit of claim 10, wherein the firstcomposition comprises about 550 IU to about 1650 IU of vitamin A, about300 IU to about 900 IU of beta carotene, about 1.0 mg to about 3.0 mg ofvitamin B₁, about 1.0 mg to about 3.0 mg of vitamin B₂, about 7.0 mg toabout 23 mg of vitamin B₃, about 1.0 mg to about 4.0 mg of vitamin B₆,about 0.5 mg to about 1.5 mg of vitamin B₉, about 2.0 mcg to about 8.0mcg of vitamin B₁₂, about 30 mg to about 90 mg of vitamin C, about 200IU to about 600 IU of vitamin D₃, about 15 IU to about 45 IU of vitaminE, about 14 mg to about 44 mg of iron, about 12 mg to about 38 mg ofmagnesium and about 7.0 mg to about 23 mg of zinc.
 12. The kit of claim1, wherein the omega-3 fatty acids is not derived from a fish oil. 13.The kit of claim 12, wherein said omega-3 fatty acids comprisedocahexaenoic acid (DHA).
 14. The kit of claim 12, wherein saiddocahexaenoic acid is derived from algae.
 15. The kit of claim 1,wherein said first composition and said second composition are packagedfor co-administration to said patient at the same time.
 16. The kit ofclaim 1, wherein said first composition and said second composition arepackaged for co-administration to said patient, wherein one saidcomposition is administered before the other said composition, in eitherorder.
 17. The kit of claim 1, wherein said first composition and saidsecond composition are packaged for administration to said patientorally.
 18. The kit of claim 1, wherein one or both of said first andsaid second composition is in a swallowable form.
 19. The kit of claim1, wherein said omega-3 fatty acids are enclosed within a gel-cap. 20.The kit of claim 1, wherein said second composition is in liquid form.21. The kit of claim 1, wherein said first composition comprises about1100 IU of vitamin A; about 600 IU beta carotene; about 400 IU ofvitamin D₃; about 60 mg of vitamin C; about 30 IU of vitamin E; about1.0 mg of vitamin B₉; about 1.6 mg of vitamin B₁; about 1.8 mg ofvitamin B₂; about 15 mg of vitamin B₃; about 2.5 mg of vitamin B₆; about5.0 mcg of vitamin B₁₂; about 29 mg of iron; about 25 mg of magnesium;and about 15 mg of zinc.
 22. The kit of claim 1, wherein said omega-3fatty acids are present in the amount of about 125 mg to about 375 mg.23. The kit of claim 1, wherein said omega-3 fatty acids are present inthe amount of about 200 mg to about 300 mg.
 24. The kit of claim 1,wherein said omega-3 fatty acids are present in the amount of about 225mg to about 275 mg.
 25. The kit of claim 1, wherein said omega-3 fattyacids are present in the amount of about 250 mg.
 26. The kit of claim 1,wherein said packaging is selected from the group consisting of bottlesand blister packs.
 27. The kit of claim 26, wherein said blister packsare sold together and said blister packs comprise a first blister packcontaining said first composition and a second blister pack containingsaid second composition.
 28. The kit of claim 26, wherein said blisterpack contains both said first composition and said second compositionpaired together per unit dose.
 29. The kit of claim 26, wherein saidblister packs are sold separately and said blister packs comprise afirst blister pack containing said first composition and a secondblister pack containing said second composition.
 30. A method comprisingproviding the kit of claim 1 to patients.